Host factors and HIV-1 replication: Clinical evidence and potential therapeutic approaches

Frontiers in Immunology

Volumn 4, Issue , 2013, Pages

  Santa Marta, Mariana ^a,b   Brito, Paula Matos de ^a,b   Godinho Santos, Ana ^a,b   Goncalves, Joao ^a,b  

^a RESEARCH INSTITUTE FOR MEDICINES IMED ULISBOA   (Portugal)

^b INSTITUTO DE MEDICINA MOLECULAR   (Portugal)

Author keywords

APOBEC; Chemokine; Chemokine receptors; Human immunodeficiency virus; Nonprogressors; SAMHD1; Tetherin; TRIM

Indexed keywords

APLAVIROC; APOLIPOPROTEIN B MRNA EDITING ENZYME CATALYTIC POLYPEPTIDE LIKE; CELL PROTEIN; CENICRIVIROC; CHEMOKINE RECEPTOR; HUMAN MONOCLONAL ANTIBODY; MARAVIROC; MEMBRANE PROTEIN; RANTES; TRIPARTITE MOTIF PROTEIN 5; VICRIVIROC;

ANTIVIRAL THERAPY; ARTICLE; CHROMOSOMAL MAPPING; DNA POLYMORPHISM; EVIDENCE BASED MEDICINE; GENE EXPRESSION; GENE SILENCING; GENETIC VARIABILITY; GENOME-WIDE ASSOCIATION STUDY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; NONHUMAN; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); RANDOMIZED CONTROLLED TRIAL (TOPIC); SIGNAL TRANSDUCTION; VIRAL GENE THERAPY; VIRUS ENTRY; VIRUS INHIBITION; VIRUS REPLICATION; VIRUS TRANSMISSION;

EID: 84975072486     PISSN: None     EISSN: 16643224     Source Type: Journal    
DOI: 10.3389/fimmu.2013.00343     Document Type: Article

References (296)

1. Deeks SG, Walker BD. Human immunodeficiency virus controllers: mechanisms of durable virus control in the absence of antiretroviral therapy. Immunity (2007) 27:406-16. doi:10.1016/j. immuni.2007.08.010
2. Balotta C, Bagnarelli P, Violin M, Ridolfo AL, Zhou D, Berlusconi A, et al. Homozygous delta 32 deletion of the CCR-5 chemokine receptor gene in an HIV-1-infected patient. AIDS (1997) 11:F67-71. doi:10.1097/00002030-199710000-00001
3. Hardie RA, Knight E, Bruneau B, Semeniuk C, Gill K, Nagelkerke N, et al. A common human leucocyte antigen-DP genotype is associated with resistance to HIV-1 infection in Kenyan sex workers. AIDS (2008) 22:2038-42. doi:10.1097/QAD. 0b013e328311d1a0
4. MacDonaldKS,FowkeKR,Kimani J, Dunand VA, Nagelkerke NJ, Ball TB, et al. Influence of HLA supertypes on susceptibility and resistance to human immunodeficiency virus type 1 infection. J Infect Dis (2000) 181:1581-9. doi: 10.1086/315472
5. van MD, van't Wout AB, Schuitemaker H. Genome-wide association studies on HIV susceptibility, pathogenesis and pharmacogenomics. Retrovirology (2012) 9:70. doi:10.1186/1742-4690-9-70
6. Alkhatib G. The biology of CCR5 and CXCR4. Curr Opin HIV AIDS (2009) 4:96-103. doi:10. 1097/COH.0b013e328324bbec
7. Samson M, Labbe O, Mollereau C, Vassart G, Parmentier M. Molecular cloning and functional expression of a new human CC-chemokine receptor gene. Biochemistry (1996) 35:3362-7. doi: 10.1021/bi952950g
8. Cocchi F, DeVico AL, Garzino-Demo A, Arya SK, Gallo RC, LussoP.Identificationof RANTES, MIP-1 alpha, and MIP-1 beta as the major HIV-suppressive factors produced by CD8+ T cells. Science (1995) 270:1811-5. doi:10. 1126/science.270.5243.1811
9. Bleul CC, Wu L, Hoxie J, Springer T, Mackay CR. The HIV core-ceptors CXCR4 and CCR5 are differentially expressed and regulated on human T lymphocytes. Proc Natl Acad Sci U S A (1997) 94: 1925-30. doi:10.1073/pnas.94.5. 1925
10. Wu L, Paxton W, Kassam N, Ruffing N, Rottman JB, Sullivan N, et al. CCR5 levels and expression pattern correlate with infectability by macrophage-tropic HIV-1, in vitro. J Exp Med (1997) 185:1681-91. doi:10.1084/ jem.185.9.1681
11. Feng Y, Broder CC, Kennedy PE, Berger EA. HIV-1 entry cofac-tor: functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor. Science (1996) 272:872-7. doi:10.1126/ science.272.5263.872
12. Hoffmann C. The epidemiology of HIV coreceptor tropism.EurJ Med Res (2007) 12:385-90.
13. Lusso P. HIV and the chemokine system: 10 years later. EMBO J (2006) 25:447-56. doi:10.1038/sj. emboj.7600947
14. Ma Q, Jones D, Borghesani PR, Segal RA, Nagasawa T, Kishimoto T, et al. Impaired B-lymphopoiesis, myelopoiesis, and derailed cere-bellar neuron migration in C. Proc Natl Acad Sci U S A (1998) 95:9448-53. doi:10.1073/pnas.95. 16.9448
15. Cohen OJ, Paolucci S, Bende SM, DaucherM,MoriuchiH,Moriuchi M,et al. CXCR4 and CCR5 genetic polymorphisms in long-term non-progressive human immunodeficiency virus infection: lack of association with mutations other than CCR5-Delta32. J Virol (1998) 72:6215-7.
16. Pollakis G, Paxton WA. Use of (alternative) coreceptors for HIV entry. Curr Opin HIV AIDS (2012) 7:440-9. doi:10.1097/ COH.0b013e328356e9f3
17. Gorry PR, Zhang C, Wu S, Kun-stman K, Trachtenberg E, Phair J, et al. Persistence of dual-tropic HIV-1 in an individual homozy-gous for the CCR5 delta 32 allele. Lancet (2002) 359:1832-4. doi:10. 1016/S0140-6736(02)08681-6
18. Gray L, Churchill MJ, Keane N, Sterjovski J, Ellett AM, Purcell DF, et al. Genetic and functional analysis of R5X4 human immunodeficiency virus type 1 envelope glycoproteins derived from two individuals homozygous for the CCR5delta32 allele. J Virol (2006) 80:3684-91. doi:10.1128/JVI.80.7. 3684-3691.2006
19. Heiken H, Becker S, Bastisch I, Schmidt RE. HIV-1 infection in a heterosexual man homozygous for CCR-5 delta32. AIDS (1999) 13:529-30. doi:10.1097/ 00002030-199903110-00017
20. Iversen AK, Christiansen CB, Attermann J, Eugen-Olsen J, Schulman S, Berntorp E, et al. Limited protective effect of the CCR5Delta32/CCR5Delta32 genotype on human immunodeficiency virus infection incidence in a cohort of patients with hemophilia and selection for genotypic X4 virus. J Infect Dis (2003) 187:215-25. doi: 10.1086/345881
21. Kuipers H, Workman C, Dyer W, Geczy A, Sullivan J, Oel-richs R. An HIV-1-infected individual homozygous for the CCR-5 delta32 allele and the SDF-1 3;A allele. AIDS (1999) 13:433-4. doi: 10.1097/00002030-199902250-00025
22. O'Brien TR, Winkler C, Dean M, Nelson JA, Carrington M, Michael NL, et al. HIV-1 infection in a man homozygous for CCR5 delta 32. Lancet (1997) 349:1219. doi: 10.1016/S0140-6736(97) 24017-1
23. Oh DY, Jessen H, Kucherer C, Neumann K, Oh N, Poggensee G, et al. CCR5Delta32 genotypes in a German HIV-1 seroconverter cohort and report of HIV-1 infection in a CCR5Delta32 homozygous individual. PLoS ONE (2008) 3:e2747. doi:10.1371/ journal.pone.0002747
24. Sheppard HW, Celum C, Michael NL, O'Brien S, Dean M, Car-rington M, et al. HIV-1 infection in individuals with the CCR5-Delta32/Delta32 genotype: acquisition of syncytium-inducing virus at seroconversion. J Acquir Immune Defic Syndr (2002) 29:307-13. doi:10.1097/ 00126334-200203010-00013
25. Theodorou I, Meyer L, Magierowska M, Katlama C, Rouzioux C. HIV-1 infection in an individual homozygous for CCR5 delta 32. Seroco Study Group. Lancet (1997) 349:1219-20. doi: 10.1016/S0140-6736(05)62411-7
26. Dean M, Carrington M, Winkler C, Huttley GA, Smith MW, Allik-mets R, et al. Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele of the CKR5 structural gene. Science (1996) 273: 1856-62. doi:10.1126/science.273. 5283.1856
27. Eugen-Olsen J, Iversen AK, Garred P, Koppelhus U, Pedersen C, Benfield TL, et al. Heterozy-gosity for a deletion in the CKR-5 gene leads to prolonged AIDS-free survival and slower CD4 T-cell decline in a cohort of HIV-seropositive individuals. AIDS (1997) 11:305-10. doi:10. 1097/00002030-199703110-00007
28. Huang Y, Paxton WA, Wolin-sky SM, Neumann AU, Zhang L, He T, et al. The role of a mutant CCR5 allele in HIV-1 transmission and disease progression. Nat Med (1996) 2:1240-3. doi:10.1038/nm1196-1240
29. Zimmerman P, Buckler W, Alkhatib G, Spalding T, Kubofcik J, Combadiere C, et al. Inherited resistance to HIV-1 conferred by an inactivating mutation in CC chemokine receptor 5: studies in populations with contrasting clinical phenotypes, defined racial background, and quantified risk. Mol Med (1997) 3:23-36.
30. Cohen OJ, Vaccarezza M,Lam GK, Baird BF, Wildt K, Murphy PM, et al. Heterozygosity for a defective gene for CC chemokine receptor 5 is not the sole determinant for the immunologic and virologic phenotype of HIV-infected long-term nonprogressors. J Clin Invest (1997) 100:1581-9. doi:10.1172/ JCI119682
31. Schinkel J, Langendam MW, Coutinho RA, Krol A, Brouwer M, Schuitemaker H. No evidence for an effect of the CCR5 delta32/+ and CCR2b 64I/+ mutations on human immunodeficiency virus (HIV)-1 disease progression among HIV-1-infected injecting drug users. J Infect Dis (1999) 179:825-31. doi:10.1086/314658
32. Wilkinson DA, Operskalski EA, Busch MP, Mosley JW, Koup RA. A 32-bp deletion within the CCR5 locus protects against transmission of parenterally acquired human immunodeficiency virus but does not affect progression to AIDS-defining illness. J Infect Dis (1998) 178:1163-6. doi:10.1086/515675
33. BorinskayaSA, KozhekbaevaZhm, Zalesov AV, Olseeva EV, Maksi-mov AR, Kutsev SI, et al. Risk of HIV infection and lethality are decreased in CCR5del32 heterozy-gotes: focus nosocomial infection study and meta-analysis. Acta Nat (2012) 4:42-52.
34. Ioannidis JP, Rosenberg PS, Goedert JJ, Ashton LJ, Ben-field TL, Buchbinder SP, et al. Effects of CCR5-Delta32, CCR2-64I, and SDF-1 3;A alleles on HIV-1 disease progression: an international meta-analysis of individual-patient data. Ann Intern Med (2001) 135:782-95. doi:10.7326/0003-4819-135-9-200111060-00008
35. Fellay J, Ge D, Shianna KV, Colombo S, Ledergerber B, Cir-ulli ET, et al. Common genetic variation and the control of HIV-1 in humans. PLoS Genet (2009) 5:e1000791. doi:10.1371/journal. pgen.1000791
36. PereyraF, JiaX, McLaren PJ, Telenti A, de Bakker PI, Walker BD, et al. The major genetic determinants of HIV-1 control affect HLA class I peptide presentation. Science (2010) 330:1551-7. doi:10. 1126/science.1195271
37. Quillent C, Oberlin E, Braun J, Rousset D, Gonzalez-Canali G, Mãtais P, et al. HIV-1-resistance phenotype conferred by combination of two separate inherited mutations of CCR5 gene. Lancet (1998) 351:14-8. doi:10. 1016/S0140-6736(97)09185-X
38. Clegg AO, Ashton LJ, Biti RA, Badhwar P, Williamson P, Kaldor JM, et al. CCR5 promoter polymorphisms, CCR559029A and CCR5 59353C, are under represented in HIV-1-infected long-term non-progressors. the Australian Long-Term Non-Progressor Study Group. AIDS (2000)14:103-8. doi:10.1097/00002030-200001280-00004
39. Knudsen TB, Kristiansen TB, Katzenstein TL, Eugen-Olsen J. Adverse effect of the CCR5 promoter-2459A allele on HIV-1 disease progression. J Med Virol (2001)65:441-4. doi:10.1002/jmv.2054.abs
40. McDermott DH, Zimmerman P, Guignard F, Kleeberger C, Leit-man SF, Murphy PM. CCR5 promoter polymorphism and HIV-1 disease progression. Lancet (1998) 352:866-70. doi:10.1016/ S0140-6736(98)04158-0
41. Hladik F, Liu H, Speelmon E, Livingston-Rosanoff D, Wilson S, Sakchalathorn P, et al. Combined effect of CCR5-Delta32 het-erozygosity and the CCR5 promoter polymorphism -2459 A/G on CCR5 expression and resistance to human immunodeficiencyvirus type 1 transmission. J Virol (2005) 79:11677-84. doi:10.1128/JVI.79. 18.11677-11684.2005
42. Salkowitz JR, Bruse SE, Meyer-son H, Valdez H, Mosier DE, Harding CV, et al. CCR5 promoter polymorphism determines macrophage CCR5 density and magnitude of HIV-1 propagation in vitro. Clin Immunol (2003) 108:234-40. doi:10.1016/ S1521-6616(03)00147-5
43. Jang DH, Choi BS, Kim SS. The effects of RANTES/CCR5 promoter polymorphisms on HIV disease progression in HIV-infected Koreans. Int J Immunogenet (2008) 35:101-5. doi:10.1111/j.1744-313X.2007. 00743.x
44. Martin MP, Dean M, Smith MW, Winkler C, Gerrard B, Michael NL, et al. Genetic acceleration of AIDS progression by a promoter variant of CCR5. Science (1998) 282:1907-11. doi:10.1126/science. 282.5395.1907
45. Easterbrook PJ, Rostron T, Ives N, Troop M, Gazzard BG, Rowland-Jones SL. Chemokine receptor polymorphisms and humanimmunodeficiency virus disease progression. J Infect Dis (1999) 180:1096-105. doi:10.1086/314997
46. El-Asmar L, Springael JY, Ballet S, Andrieu EU, Vassart G, Par-mentier M. Evidence for negative binding cooperativity within CCR5-CCR2b heterodimers. Mol Pharmacol (2005) 67:460-9. doi: 10.1124/mol.104.003624
47. Hernanz-Falcon P, Rodriguez-Frade JM, Serrano A, Juan D, del SA, Soriano SF, et al. Identification of amino acid residues crucial for chemokine receptor dimerization. Nat Immunol (2004) 5:216-23. doi:10.1038/ni1027
48. Issafras H, Angers S, Bulenger S, Blanpain C, Parmentier M, Labbe-Jullie C, et al. Constitutive agonist-independent CCR5 oligomeriza-tion and antibody-mediated clustering occurring at physiological levels of receptors. J Biol Chem (2002) 277:34666-73. doi: 10.1074/jbc.M202386200
49. Mellado M, Rodriguez-Frade JM, Vila-Coro AJ, Fernandez S, Martin de AA, Jones DR, et al. Chemokine receptor homo- or heterodimer-ization activates distinct signaling pathways. EMBO J (2001) 20:2497-507. doi:10.1093/emboj/ 20.10.2497
50. Sohy D, Parmentier M, Springael JY. Allosteric transinhibition by specific antagonists in CCR2/CXCR4heterodimers. J Biol Chem (2007) 282:30062-9. doi:10.1074/jbc.M705302200
51. LeeB,Doranz BJ,RanaS,YiY,Mel-lado M, Frade JM, et al. Influence of the CCR2-V64I polymorphism on human immunodeficiency virus type 1 coreceptor activity and on chemokine receptor function of CCR2b, CCR3, CCR5, and CXCR4. J Virol (1998) 72:7450-8.
52. Anzala AO, Ball TB, Rostron T, O'Brien SJ, Plummer FA, Rowland-Jones SL. CCR2-64I allele and genotype association with delayed AIDS progression in African women. University of Nairobi Collaboration for HIV Research. Lancet (1998) 351:1632-3. doi:10.1016/S0140-6736(05)77688-1
53. Mulherin SA, O'Brien TR, Ioan-nidis JP, Goedert JJ, Buchbinder SP, Coutinho RA, et al. Effects of CCR5-Delta32 and CCR2-64I alleles on HIV-1 disease progression: the protection varies with duration of infection. AIDS (2003) 17:377-87. doi:10.1097/ 00002030-200302140-00012
54. Puissant Bã, Roubinet F, Mas-sip P, Sandres-Saune K, Apoil PA, Abbal M, et al. Analysis of CCR5, CCR2, CX3CR1, and SDF1 polymorphisms in HIV-positive treated patients: impact on response to HAART and on peripheral T lymphocyte counts. AIDS Res Hum Retroviruses (2006) 22:153-62. doi:10.1089/aid.2006. 22.153
55. Rizzardi GP,Morawetz RA,Vicenzi E, Ghezzi S, Poli G, Lazzarin A, et al. CCR2 polymorphism and HIV disease. Swiss HIV Cohort. Nat Med (1998) 4:252-3. doi:10.1038/ nm0398-252
56. Smith MW, Dean M, Carring-ton M, Winkler C, Huttley GA, Lomb DA, et al. Contrasting genetic influence of CCR2 and CCR5 variants on HIV-1 infection and disease progression. Hemophilia Growth and Development Study (HGDS), Multicenter AIDS Cohort Study (MACS), Multicenter Hemophilia Cohort Study (MHCS), San Francisco City Cohort. Science (1997) 277:959-65. doi:10.1126/science.277.5328.959
57. Kostrikis LG, Huang Y, Moore JP, Wolinsky SM,ZhangL,GuoY,etal. A chemokine receptor CCR2 allele delays HIV-1 disease progression and is associated with a CCR5 promoter mutation. Nat Med (1998) 4:350-3. doi:10.1038/ nm0398-350
58. Suresh P, Wanchu A, Sachdeva RK, Bhatnagar A. Gene polymorphisms in CCR5, CCR2, CX3CR1, SDF-1 and RANTES in exposed but uninfected partners of HIV-1 infected individuals in North India. J Clin Immunol (2006) 26:476-84. doi:10.1007/s10875-006-9036-0
59. Sriwanthana B, Hodge T, Mas-tro TD, Dezzutti CS, Bond K, Stephens HA, et al. HIV-specific cytotoxic T lymphocytes, HLA-A11, and chemokine-related factors may act synergistically to determine HIV resistance in CCR5 delta32-negative female sex workers in Chiang Rai, Northern Thailand. AIDS Res Hum Retroviruses (2001) 17:719-34. doi:10.1089/ 088922201750236997
60. Louisirirotchanakul S, Liu H, Roongpisuthipong A, Nakayama EE, Takebe Y, Shioda T, et al. Genetic analysis of HIV-1 discordant couples in Thailand: association of CCR2 64I homozygos-ity with HIV-1-negative status. J Acquir Immune Defic Syndr (2002) 29:314-5. doi:10.1097/00126334-200203010-00014
61. Nakayama EE, Tanaka Y, Nagai Y, Iwamoto A, Shioda T. A CCR2-V64I polymorphism affects stability of CCR2A isoform. AIDS (2004) 18:729-38. doi:10.1097/00002030-200403260-00003
62. Berger E, Murphy PM, Far-ber JM. Chemokine receptors as HIV-1 coreceptors: roles in viral entry, tropism, and disease. Annu Rev Immunol (1999) 17:657-700. doi:10.1146/annurev. immunol.17.1.657
63. O'Brien SJ, Moore JP. The effect of genetic variation in chemokines and their receptors on HIV transmission and progression to AIDS. Immunol Rev (2000) 177:99-111. doi:10.1034/j.1600-065X.2000. 17710.x
64. Rodriguez-Frade JM, del RG, Serrano A, Hernanz-Falcon P, Soriano SF, Vila-Coro AJ, et al. Blocking HIV-1 infection via CCR5 and CXCR4receptorsbyactingintrans on the CCR2 chemokine receptor. EMBO J (2004) 23:66-76. doi:10. 1038/sj.emboj.7600020
65. Zhao Q. Dual targeting of CCR2 and CCR5: therapeutic potential for immunologic and cardiovascular diseases. J Leukoc Biol (2010) 88:41-55. doi:10.1189/jlb.1009671
66. Limou S, Coulonges Cã, Her-beck JT, van Manen D, An P, Le Clerc S, et al. Multiple-cohort genetic association study reveals CXCR6 asa new chemokine receptor involved in long-term non-progression to AIDS. J Infect Dis (2010) 202:908-15. doi:10.1086/ 655782
67. Duggal P, An P, Beaty TH, Strathdee S, Farzadegan H, Markham RB, et al. Genetic influence of CXCR6 chemokine receptor alleles on PCP-mediated AIDS progression among African Americans. Genes Immun (2003) 4:245-50. doi:10.1038/sj.gene.6363950
68. Petit SJ, Chayen NE, Pease JE. Site-directed mutagenesis of the chemokine receptor CXCR6 suggests a novel paradigm for interactions with the ligand CXCL16. Eur J Immunol (2008) 38:2337-50.doi:10.1002/eji. 200838269
69. Passam AM, Sourvinos G, Kram-bovitis E, Miyakis S, Stavrianeas N, Zagoreos I, et al. Polymorphisms of Cx(3)CR1 and CXCR6 receptors in relation to HAART therapy of HIV type 1 patients. AIDS Res Hum Retroviruses (2007) 23:1026-32. doi:10.1089/aid.2006. 0248
70. Faure S, Meyer L, Costagliola D, Vaneensberghe C, Genin E, Autran B, et al. Rapid progression to AIDS in HIV+ individuals with a structural variant of the chemokine receptor CX3CR1. Science (2000) 287:2274-7. doi:10. 1126/science.287.5461.2274
71. Haas G, Samri A, Gomard E, Hos-malin A, Duntze J, Bouley JM, et al. Cytotoxic T-cell responses to HIV-1 reverse transcriptase, integrase and protease. AIDS (1998)12:1427-36. doi:10.1097/00002030-199812000-00004
72. Magierowska M, Theodorou I, Debrã P, Sanson F, Autran B, Riviã Y, et al. Combined geno types of CCR5, CCR2, SDF1, and HLA genes can predict the long-term nonprogressor status in human immunodeficiency virus-1-infected individuals. Blood (1999)93:936-41.
73. Meyer L, Magierowska M, Hubert JB, Rouzioux C, Deveau C, San-son F, et al. Early protective effect of CCR-5 delta 32 heterozygos-ity on HIV-1 disease progression: relationship with viral load. The SEROCO Study Group. AIDS (1997) 11:F73-8.
74. McDermott DH. Genetic polymorphism in CX3CR1 and risk of HIV disease. Science (2000) 290:2031a-22031a. doi:10.1126/ science.290.5499.2031a
75. Hendel H, Cho YY, Gauthier N, Rappaport J, Schachter F, Zagury JF. Contribution of cohort studies in understanding HIV pathogen-esis: introduction of the GRIV cohort and preliminary results. Biomed Pharmacother (1996) 50:480-7. doi:10.1016/S0753-3322(97)89278-5
76. Vidal F, Viladã C, Domingo P, Broch M, Pedrol E, Dalmau D, et al. Spanish HIV-1-infected long-term nonprogressors of more than 15 years have an increased frequency of the CX3CR1 249I variant allele. J Acquir Immune Defic Syndr (2005) 40:527-31. doi:10.1097/01.qai.0000186362. 50457.e0
77. Modi WS, Lautenberger J, An P, Scott K, Goedert JJ, Kirk GD, et al. Genetic variation in the CCL18-CCL3-CCL4 chemokine gene cluster influences HIV Type 1 transmission and AIDS disease progression. Am J Hum Genet (2006) 79:120-8. doi:10.1086/505331
78. Blanpain C, Migeotte I, Lee B, Vakili J, Doranz BJ, Govaerts C, et al. CCR5 binds multiple CC-chemokines: MCP-3 acts as a natural antagonist. Blood (1999) 94:1899-905.
79. Piacentini L, Biasin M, Fenizia C, Clerici M. Genetic correlates of protection against HIV infection: the ally within. J Intern Med (2009) 265:110-24. doi:10.1111/j.1365-2796.2008.02041.x
80. Saha K, Bentsman G, Chess L, David J. Endogenous production of l2-chemokines by CD4 +, but Not CD8 +, t-cell clones correlates with the clinical state of human immunodeficiency virus type 1 (HIV-1)-infected individuals and may be responsible for blocking infection with nonsyncytium-induc. J Virol (1998) 72:876-81.
81. Nakajima T, Kaur G, Mehra N, Kimura A. HIV-1/AIDS susceptibility and copy number variation in CCL3L1, a gene encoding a natural ligand for HIV-1 co-receptor CCR5. Cytogenet Genome Res (2008) 123:156-60. doi:10. 1159/000184703
82. Gonzalez E, Kulkarni H, Bolivar H, Mangano A, Sanchez R, Catano G, et al. The influence of CCL3L1 gene-containing segmental duplications on HIV-1/AIDS susceptibility. Science (2005) 307:1434-40. doi:10.1126/science.1101160
83. Liu S, Yao L, Ding D, Zhu H. CCL3L1 copy number variation and susceptibility to HIV-1 infection: a meta-analysis. PLoS ONE (2010)5:e15778. doi:10.1371/journal.pone.0015778
84. Rathore A, Chatterjee A, Sivarama P, Yamamoto N, Singhal PK, Dhole TN. Association of CCR5-59029 A/G and CCL3L1 copy number polymorphism with HIV type 1 transmission/progression among HIV type 1-seropositive and repeatedly sexually exposed HIV type 1-seronegative North Indians. AIDS Res Hum Retro-viruses (2009) 25:1149-56. doi:10. 1089/aid.2008.0019
85. Gaertner H, Cerini F, Escola JM, KuenziG,MelottiA,Offord R,etal. Highly potent, fully recombinant anti-HIV chemokines: reengineer-ing a low-cost microbicide. Proc Natl Acad Sci U S A (2008) 105:17706-11. doi:10.1073/pnas. 0805098105
86. Hartley O, Gaertner H, Wilken J, Thompson D, Fish R, Ramos A, et al. Medicinal chemistry applied to a synthetic protein: development of highly potent HIV entry inhibitors. Proc Natl Acad Sci U S A (2004) 101:16460-5. doi:10.1073/ pnas.0404802101
87. Toossi Z, Mayanja-Kizza H, Baseke J, Peters P, Wu M, Abraha A, et al. Inhibition of human immunodeficiency virus-1 (HIV-1) by beta-chemokine analogues in mononuclear cells from HIV-1-infected patients with active tuberculosis. Clin Exp Immunol (2005) 142:327-32. doi:10.1111/j. 1365-2249.2005.02913.x
88. Lederman MM, Veazey RS, Offord R, Mosier DE, Dufour J, Mef-ford M, et al. Prevention of vaginal SHIV transmission in rhesus macaques through inhibition of CCR5. Science (2004) 306:485-7. doi:10.1126/science.1099288
89. Veazey RS, Ling B, Green LC, Ribka EP, Lifson JD, Piatak M Jr., et al. Topically applied recombi-nant chemokine analogues fully protect macaques from vaginal simian-human immunodeficiency virus challenge. J Infect Dis (2009) 199:1525-7. doi:10.1086/598685
90. Liu H, Chao D, Nakayama EE, Taguchi H, Goto M, Xin X, et al. Polymorphism in RANTES chemokine promoter affects HIV-1 disease progression. Proc Natl Acad Sci U S A (1999) 96: 4581-5. doi:10.1073/pnas.96.8. 4581
91. McDermott DH, Beecroft MJ, Kleeberger CA, Al-Sharif FM, Ollier WE, Zimmerman PA, et al. Chemokine RANTES promoter polymorphism affects risk of both HIV infection and disease progression in the multi-center AIDS Cohort Study. AIDS (2000) 14:2671-8. doi:10.1097/ 00002030-200012010-00006
92. Vidal F, Peraire J, Domingo P, Broch M, Cairo M, Pedrol E, et al. Polymorphism of RANTES chemokine gene promoter is not associated with long-term nonprogressive HIV-1 infection of more than 16 years. J Acquir Immune Defic Syndr (2006) 41:17-22.doi:10.1097/01.qai. 0000188335.86466.ea
93. An P, Nelson GW, Wang L, Donfield S, Goedert JJ, Phair J, et al. Modulating influence on HIV/AIDSbyinteracting RANTES gene variants. Proc Natl Acad Sci U S A (2002) 99:10002-7. doi:10. 1073/pnas.142313799
94. Bleul CC, Farzan M, Choe H, Parolin C, Clark-Lewis I, Sodroski J, et al. The lymphocyte chemoat-tractant SDF-1 is a ligand for LESTR/fusin and blocks HIV-1 entry. Nature (1996) 382:829-33. doi:10.1038/382829a0
95. Oberlin E, Amara A, Bachelerie F, Bessia C, Virelizier JL, Arenzana-Seisdedos F, et al. The CXC chemokine SDF-1 is the ligand for LESTR/fusin and prevents infection by T-cell-line-adapted HIV-1. Nature (1996) 382:833-5. doi:10. 1038/382833a
96. Amara A, Gall SL, Schwartz O, Salamero J, Montes M, Loetscher P, et al. HIV coreceptor downregu-lation as antiviral principle: SDF-1alpha-dependent internalization of the chemokine receptor CXCR4 contributes to inhibition of HIV replication. J Exp Med (1997) 186:139-46. doi:10.1084/jem.186. 1.139
97. Signoret N, Oldridge J, Pelchen-Matthews A, Klasse PJ, Tran T, Brass LF, et al. Phorbol esters and SDF-1 induce rapid endo-cytosis and down modulation of the chemokine receptor CXCR4. J Cell Biol (1997) 139:651-64. doi: 10.1083/jcb.139.3.651
98. Hendel H, Henon N, Lebuanec H, Lachgar A, Poncelet H, Caillat-Zucman S, et al. Distinctive effects of CCR5, CCR2, and SDF1 genetic polymorphisms in AIDS progression. J Acquir Immune DeficSyndrHum Retrovirol (1998) 19:381-6. doi: 10.1097/00042560-199812010-00009
99. Mahajan SD, Agosto-Mojica A, Aalinkeel R, Reynolds JL, Nair BB, Sykes DE, et al. Role of chemokine and cytokine polymorphisms in the progression of HIV-1 disease. Biochem Biophys Res Com-mun (2010) 396:348-52. doi:10. 1016/j.bbrc.2010.04.095
100. Winkler C, Modi W, Smith MW, Nelson GW, Wu X, Carring-ton M, et al. Genetic restriction of AIDS pathogenesis by an SDF-1 chemokine gene variant. ALIVE Study, Hemophilia Growth and Development Study (HGDS), Multicenter AIDS Cohort Study (MACS), Multicenter Hemophilia Cohort Study (MHCS), San Francisco City Cohort (SFCC). Science (1998) 279:389-93. doi:10.1126/ science.279.5349.389
101. Soriano A, Martínez C, García F, Plana M, Palou E, Lejeune MN, et al. Plasma stromal cell-derived factor (SDF)-1 levels,SDF1-3;Ageno-type, and expression of CXCR4 on T lymphocytes: their impact on resistance to human immunodeficiency virus type 1 infection and its progression. J Infect Dis (2002) 186:922-31. doi:10.1086/343741
102. van Rij RP, Broersen S, Goudsmit J, Coutinho RA, Schuitemaker H. The role of a stromal cell-derived factor-1 chemokine gene variant in the clinical course of HIV-1 infection. AIDS (1998) 12:F85-90. doi:10.1097/ 00002030-199809000-00002
103. Vidal F, Peraire J, Domingo P, Broch M, Knobel H, Pedrol E, et al. Lack of association of SDF-1 3;A variant allele with long-term nonprogressive HIV-1 infection is extended beyond 16 years. J Acquir Immune Defic Syndr (2005) 40:276-9. doi:10.1097/01. qai.0000176653.89769.4d
104. Wang FS, Hong WG, Cao Y, Liu MX, Jin L, Hu LP, et al. Population survey of CCR5 delta32, CCR5 m303, CCR2b 64I, and SDF1 3;A allele frequencies in indigenous Chinese healthy individuals, and in HIV-1-infected and HIV-1-uninfected individuals in HIV-1 risk groups. J Acquir Immune Defic Syndr (2003) 32:124-30. doi:10. 1097/00126334-200302010-00002
105. Nichols WG, Steel HM, Bonny T, Adkison K, Curtis L, Millard J, et al. Hepatotoxicity observed in clinical trials of aplaviroc (GW873140). Antimicrob Agents Chemother (2008) 52:858-65. doi: 10.1128/AAC.00821-07
106. Caseiro MM, Nelson M, Diaz RS, Gathe J, de Andrade Neto JL, Slim J, et al. Vicriviroc plus optimized background therapy for treatment-experienced subjects with CCR5 HIV-1 infection: final results of two randomized phase III trials. J Infect (2012) 65:326-35. doi: 10.1016/j.jinf.2012.05.008
107. Klibanov OM, Williams SH, Iler CA. Cenicriviroc, an orally active CCR5 antagonist for the potential treatment of HIV infection. Curr Opin Investig Drugs (2010) 11:940-50.
108. Lalezari J, Gathe J, Brinson C, Thompson M, Cohen C, Deje-sus E, et al. Safety, efficacy, and pharmacokinetics of TBR-652, a CCR5/CCR2 antagonist, in HIV-1-infected, treatment-experienced, CCR5 antagonist-naive subjects. J Acquir Immune Defic Syndr (2011) 57:118-25. doi:10.1097/ QAI.0b013e318213c2c0
109. Marier JF, Pheng L, Trinh MM, Burris HA III, Jones S, Anderson K, et al. Pharmacokinetics of SN2310, an injectable emulsion that incorporates a new derivative of SN-38 in patients with advanced solid tumors. JPharm Sci (2011) 100:4536-45. doi:10.1002/ jps.22645
110. Jacobson JM, Lalezari JP, Thompson MA, Fichtenbaum CJ, Saag MS, Zingman BS, et al. Phase 2a study of the CCR5 monoclonal antibody PRO 140 administered intravenously to HIV-infected adults. Antimicrob Agents Chemother (2010) 54:4137-42. doi:10.1128/AAC.00086-10
111. Alkhatib G,Locati M,Kennedy PE, Murphy PM, Berger EA. HIV-1 coreceptor activity of CCR5 and its inhibition by chemokines: independence from G protein signaling and importance of coreceptor downmodulation. Virology (1997) 234:340-8. doi:10.1006/viro.1997. 8673
112. Dorr P, Westby M, Dobbs S, Griffin P, Irvine B, Macartney M, et al. Maraviroc (UK-427,857), a potent, orally bioavailable, and selective small-molecule inhibitor of chemokine receptor CCR5 with broad-spectrum anti-human immunodeficiency virus type 1 activity. Antimicrob Agents Chemother (2005) 49:4721-32. doi:10.1128/AAC.49.11.4721-4732.2005
113. Jacobson JM, Thompson MA, Lalezari JP, Saag MS, Zingman BS, D'Ambrosio P, et al. Anti-HIV-1 activity of weekly or biweekly treatment with subcutaneous PRO 140,aCCR5 monoclonal antibody. J Infect Dis (2010) 201:1481-7. doi: 10.1086/652190
114. DiGiusto DL, Krishnan A, Li L, Li H. RNA-based gene therapy for HIV with lentiviral vector-modified CD34(+) cellsinpatients undergoing transplantation for AIDS-related lymphoma. Science Transl Med (2010) 2:doi:10.1126/ scitranslmed.3000931
115. Kim SS, Peer D, Kumar P, Subra-manya S, Wu H, Asthana D, et al. RNAi-mediated CCR5 silencing by LFA-1-targeted nanoparticles prevents HIV infection in BLT mice. Mol Ther (2010) 18:370-6. doi:10. 1038/mt.2009.271
116. Perez EE, Wang J, Miller JC, Jou-venot Y, Kim KA, Liu O, et al. Establishment of HIV-1 resistance in CD4+ T cells by genome editing using zinc-finger nucleases. Nat Biotechnol (2008) 26:808-16. doi: 10.1038/nbt1410
117. Swan CH, Buhler B, Steinberger P, Tschan MP, Barbas CF III, Torbett BE. T-cell protection and enrichment through lentiviral CCR5 intrabody gene delivery. Gene Ther (2006) 13:1480-92. doi:10.1038/sj. gt.3302801
118. Allers K, Hutter G, Hofmann J, Loddenkemper C, Rieger K, Thiel E, et al. Evidence for the cure of HIV infection by CCR5Delta32/Delta32 stem cell transplantation. Blood (2011) 117:2791-9. doi:10.1182/blood-2010-09-309591
119. Hutter G, Nowak D, Mossner M, Ganepola S, Mussig A, Allers K, et al. Long-term control of HIV by CCR5 Delta32/Delta32 stem-cell transplantation. N Engl J Med (2009) 360:692-8. doi:10. 1056/NEJMoa0802905
120. Shimizu S, Hong P, Arumugam B, Pokomo L, Boyer J, Koizumi N, et al. A highly efficient short hairpin RNA potently down-regulates CCR5 expression in systemic lymphoid organs in the hu-BLT mouse model. Blood (2010) 115:1534-44. doi:10.1182/blood-2009-04-215855
121. Carroll D. Genome engineering with zinc-finger nucleases. Genetics (2011) 188:773-82. doi:10. 1534/genetics.111.131433
122. Holt N, Wang J, Kim K, Friedman G, Wang X, Taupin V, et al. Human hematopoietic stem/progenitor cells modified by zinc-finger nucleases targeted to CCR5 control HIV-1 in vivo. Nat Biotechnol (2010) 28:839-47. doi:10.1038/nbt.1663
123. Conticello SG. The AID/APOBEC family of nucleic acid mutators. Genome Biol (2008) 9:229. doi:10. 1186/gb-2008-9-6-229
124. Pham P, Bransteitter R, Goodman MF. Reward versus risk: DNA cytidine deaminases triggering immunity and disease. Biochemistry (2005) 44:2703-15. doi: 10.1021/bi047481+
125. Chiu YL, Soros VB, Kreisberg JF, Stopak K, Yonemoto W, Greene WC. Cellular APOBEC3G restricts HIV-1 infection in resting CD4+ T cells. Nature (2005) 435:108-14. doi:10.1038/nature03493
126. Pion M, Granelli-Piperno A, Mangeat B, Stalder R, Cor-rea R, Steinman RM, et al. APOBEC3G/3F mediates intrinsic resistance of monocyte-derived dendritic cells to HIV-1 infection. J Exp Med (2006) 203:2887-93. doi:10.1084/jem.20061519
127. Stopak KS, Chiu YL, Kropp J, Grant RM, Greene WC. Distinct patterns of cytokine regulation of APOBEC3G expression and activity in primary lymphocytes, macrophages, and dendritic cells. J Biol Chem (2007) 282:3539-46. doi:10.1074/jbc.M610138200
128. ChiuYL,GreeneWC.APOBEC3G: an intracellular centurion. Phi-los Trans R Soc Lond B Biol Sci (2009) 364:689-703. doi:10.1098/ rstb.2008.0193
129. Smith HC, Bennett RP, Kizilyer A, McDougall WM, Prohaska KM. Functions and regulation of the APOBEC family of proteins. Semin Cell Dev Biol (2012) 23:258-68. doi:10.1016/j.semcdb.2011.10.004
130. Mariani R, Chen D, Schrofel-bauer B, Navarro F, Konig R, Bollman B, et al. Species-specific exclusion of APOBEC3G from HIV-1 virions by Vif. Cell (2003) 114:21-31. doi:10.1016/S0092-8674(03)00515-4
131. Stopak K, de Noronha C, Yonemoto W, Greene WC. HIV-1 Vif blocks the antiviral activity of APOBEC3G by impairing both its translation and intracel-lular stability. Mol Cell (2003) 12:591-601. doi:10.1016/S1097-2765(03)00353-8
132. Chiu YL, Witkowska HE, Hall SC, Santiago M, Soros VB, Esnault C, et al. High-molecular-mass APOBEC3G complexesrestrictAlu retrotransposition. Proc Natl Acad Sci U S A (2006) 103:15588-93. doi:10.1073/pnas.0604524103
133. Kreisberg JF, Yonemoto W, Greene WC. Endogenous factors enhance HIV infection of tissue naive CD4 T cells by stimulating high molecular mass APOBEC3G complex formation. J Exp Med (2006) 203:865-70. doi:10.1084/ jem.20051856
134. Suspene R, Sommer P, Henry M, Ferris S, Guetard D, Pochet S, et al. APOBEC3G is a single-stranded DNA cytidine deaminase and functions independently of HIV reverse transcriptase. Nucleic Acids Res (2004) 32:2421-9. doi: 10.1093/nar/gkh554
135. Yu Q, Konig R, Pillai S, Chiles K, Kearney M, Palmer S, et al. Single-strand specificity of APOBEC3G accounts for minus-strand deam-ination of the HIV genome. Nat Struct Mol Biol (2004) 11:435-42. doi:10.1038/nsmb758
136. Schrofelbauer B, Yu Q, Zeitlin SG, Landau NR. Human immunodeficiency virus type 1 Vpr induces the degradation of the UNG and SMUG uracil-DNA glycosylases. J Virol (2005) 79:10978-87. doi:10. 1128/JVI.79.17.10978-10987.2005
137. Yang B, Chen K, Zhang C, Huang S, Zhang H. Virion-associated uracil DNA glycosylase-2 and apurinic/apyrimidinic endonu-clease are involved in the degradation of APOBEC3G-edited nascent HIV-1 DNA. J Biol Chem (2007) 282:11667-75. doi:10.1074/jbc.M606864200
138. Harris RS, Bishop KN, Sheehy AM, Craig HM, Petersen-Mahrt SK, Watt IN, et al. DNA deam-ination mediates innate immunity to retroviral infection. Cell (2003) 113:803-9. doi:10.1016/ S0092-8674(03)00423-9
139. Lecossier D, Bouchonnet F, Clavel F, Hance AJ. Hyper-mutation of HIV-1 DNA in the absence of the Vif protein. Science (2003) 300:1112. doi:10.1126/science.1083338
140. Mangeat B, Turelli P, Caron G, FriedliM,PerrinL,TronoD.Broad antiretroviral defence by human APOBEC3G through lethal editing of nascent reverse transcripts. Nature (2003) 424:99-103. doi:10. 1038/nature01709
141. Zhang H, Yang B, Pomerantz RJ, Zhang C, Arunachalam SC, Gao L. The cytidine deaminase CEM15 induces hypermutation in newly synthesized HIV-1 DNA. Nature (2003) 424:94-8. doi:10. 1038/nature01707
142. Newman EN, Holmes RK, Craig HM, Klein KC, Lingappa JR, Malim MH, et al. Antiviral function of APOBEC3G can be dissociated from cytidine deaminase activity. Curr Biol (2005) 15:166-70. doi:10.1016/j.cub.2004.12.068
143. Shindo K, Takaori-Kondo A, Kobayashi M, Abudu A, Fukunaga K, Uchiyama T. The enzymatic activity of CEM15/Apobec-3G is essential for the regulation of the infectivity of HIV-1 virion but not a sole determinant of its antiviral activity. J Biol Chem (2003) 278:44412-6. doi:10.1074/jbc.C300376200
144. Mbisa JL, Barr R, Thomas JA, Vandegraaff N, Dorweiler IJ, Svarovskaia ES, et al. Human immunodeficiency virus type 1 cDNAs produced in the presence of APOBEC3G exhibit defects in plus-strand DNA transfer and integration. J Virol (2007) 81:7099-110. doi:10.1128/JVI.00272-07
145. Bishop KN, Verma M, Kim EY, Wolinsky SM, Malim MH. APOBEC3G inhibits elongation of HIV-1 reverse transcripts. PLoS Pathog (2008) 4:e1000231. doi:10. 1371/journal.ppat.1000231
146. Guo F, Cen S, Niu M, Saadat-mand J, Kleiman L. Inhibition of formula-primed reverse transcription by human APOBEC3G during human immunodeficiency virus type 1 replication. J Virol (2006) 80:11710-22. doi:10.1128/ JVI.01038-06
147. Han Y, Wang X, Dang Y, Zheng YH. APOBEC3G and APOBEC3F require an endogenous cofactor to block HIV-1 replication. PLoS Pathog (2008) 4:e1000095. doi:10. 1371/journal.ppat.1000095
148. Anderson JL, Hope TJ. APOBEC3G restricts early HIV-1 replication in the cytoplasm of target cells. Virology (2008) 375:1-12.doi:10.1016/j.virol. 2008.01.042
149. Luo K,Wang T,Liu B, Tian C,Xiao Z, Kappes J, et al. Cytidine deami-nasesAPOBEC3GandAPOBEC3F interact with human immunodeficiency virus type 1 integrase and inhibit proviral DNA formation. J Virol (2007) 81:7238-48. doi:10. 1128/JVI.02584-06
150. Mbisa JL, Bu W, Pathak VK. APOBEC3F and APOBEC3G inhibit HIV-1 DNA integration by different mechanisms. J Virol (2010) 84:5250-9. doi:10.1128/JVI.02358-09
151. Holmes RK, Koning FA, Bishop KN, Malim MH. APOBEC3F can inhibit the accumulation of HIV-1 reverse transcription products in the absence of hypermutation. Comparisons with APOBEC3G. J Biol Chem (2007) 282:2587-95. doi:10.1074/jbc.M607298200
152. Yang Y, Guo F, Cen S, Kleiman L. Inhibition of initiation of reverse transcription in HIV-1 by human APOBEC3F. Virology (2007) 365:92-100. doi:10.1016/j. virol.2007.03.022
153. Goila-GaurR,StrebelK.HIV-1Vif, APOBEC, and intrinsic immunity. Retrovirology (2008) 5:51. doi:10. 1186/1742-4690-5-51
154. Harris RS, Liddament MT. Retro-viral restriction by APOBEC proteins. Nat Rev Immunol (2004) 4:868-77. doi:10.1038/nri1489
155. Sheehy AM, Gaddis NC, Choi JD, Malim MH. Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein. Nature (2002) 418:646-50. doi:10.1038/nature00939
156. Conticello SG, Harris RS, Neu-berger MS. The Vif protein of HIV triggers degradation of the human antiretroviral DNA deaminase APOBEC3G. Curr Biol (2003)13:2009-13. doi:10.1016/j.cub.2003.10.034
157. Marin M, Rose KM, Kozak SL, Kabat D. HIV-1 Vif protein binds the editing enzyme APOBEC3G and induces its degradation. Nat Med (2003) 9:1398-403. doi:10. 1038/nm946
158. MehleA,Goncalves J,Santa-Marta M, McPike M, Gabuzda D. Phos-phorylation of a novel SOCS-box regulates assembly of the HIV-1 Vif-Cul5 complex that promotes APOBEC3G degradation. Genes Dev (2004) 18:2861-6. doi: 10.1101/gad.1249904
159. MehleA,StrackB,AncutaP,Zhang C,McPikeM,GabuzdaD.Vif overcomes the innate antiviral activity of APOBEC3G by promoting its degradation in the ubiquitin-proteasome pathway. J Biol Chem (2004) 279:7792-8. doi:10.1074/ jbc.M313093200
160. Yu X, Yu Y, Liu B, Luo K, Kong W, Mao P, et al. Induction of APOBEC3G ubiquitination and degradation by an HIV-1 Vif-Cul5-SCF complex. Science (2003) 302:1056-60. doi:10.1126/science. 1089591
161. Yu Y, Xiao Z, Ehrlich ES, Yu X, Yu XF. Selective assembly of HIV-1 Vif-Cul5-ElonginB-ElonginC E3 ubiquitin ligase complex through a novel SOCS box and upstream cysteines. Genes Dev (2004) 18:2867-72. doi:10.1101/gad.1250204
162. Du J, Zhao K, Rui Y, Li P, Zhou X, Zhang W, et al. Differential Requirements for HIV-1 Vif-mediated APOBEC3G degradation and RUNX1-mediated transcription by core binding factor beta. J Virol (2013) 87:1906-11. doi:10.1128/JVI.02199-12
163. Jager S, Kim DY, Hultquist JF, Shindo K, LaRue RS, Kwon E, et al. Vif hijacks CBF-beta to degrade APOBEC3G and promote HIV-1 infection. Nature (2012)481:371-5. doi:10.1038/nature10693
164. Kim DY, Kwon E, Hartley PD,Crosby DC, Mann S, Krogan NJ, et al. CBFbeta stabilizes HIV Vif to counteract APOBEC3 at the expense of RUNX1 target gene expression. Mol Cell (2013) 49:632-44. doi:10.1016/j.molcel.2012.12.012
165. Zhang W, Du J, Evans SL, Yu Y, Yu XF. T-cell differentiation factor CBF-beta regulates HIV-1 Vif-mediated evasion of host restriction. Nature (2012) 481:376-9. doi:10.1038/nature10718
166. Cen S, Guo F, Niu M, Saadat-mand J, Deflassieux J, Kleiman L. The interaction between HIV-1 Gag and APOBEC3G. J Biol Chem (2004) 279:33177-84. doi: 10.1074/jbc.M402062200
167. Opi S, Kao S, Goila-Gaur R, Khan MA, Miyagi E, Takeuchi H, et al. Human immunodeficiency virus type 1 Vif inhibits packaging and antiviral activity of a degradation-resistant APOBEC3G variant. J Virol (2007) 81:8236-46. doi:10. 1128/JVI.02694-06
168. Syed F, McCrae MA. Interactions in vivo between the Vif protein of HIV-1 and the precursor [Pr55(GAG)] of the virion nucleocapsid proteins. Arch Virol (2009) 154:1797-805. doi:10. 1007/s00705-009-0520-8
169. Santa-Marta M, da Silva FA, Fon-seca AM, Goncalves J. HIV-1 Vif can directly inhibit apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3G-mediated cytidine deamination by using a single amino acid interaction and without protein degradation. J Biol Chem (2005) 280:8765-75. doi:10.1074/jbc.M409309200
170. Huang Y, Zhang L, Ho DD. Characterization of gag and pol sequences from long-term survivors of human immunodeficiency virus type 1 infection. Virology (1998) 240:36-49. doi:10. 1006/viro.1997.8913
171. Janini M, Rogers M, Birx DR, McCutchan FE. Human immunodeficiency virus type 1 DNA sequences genetically damaged by hypermutation are often abundant in patient peripheral blood mononuclear cells and may be generated during near-simultaneous infection and activation of CD4(+) T cells. J Virol (2001) 75:7973-86. doi:10. 1128/JVI.75.17.7973-7986.2001
172. Kao S, Miyagi E, Khan MA, Takeuchi H, Opi S, Goila-Gaur R, et al. Production of infectious human immunodeficiency virus type 1 does not require depletion of APOBEC3G from virus-producing cells. Retrovirol-ogy (2004) 1:27. doi:10.1186/ 1742-4690-1-27
173. Kieffer TL, Kwon P, Nettles RE, Han Y, Ray SC, Siliciano RF. G →A hypermutation in protease and reverse transcriptase regions of human immunodeficiency virus type 1 residing in resting CD4+ T cells in vivo. J Virol (2005) 79:1975-80. doi:10.1128/JVI.79.3. 1975-1980.2005
174. Pace C, Keller J, Nolan D, James I, Gaudieri S, Moore C, et al. Population level analysis of human immunodeficiency virus type 1 hypermutation and its relationship with APOBEC3G and vif genetic variation. J Virol (2006) 80:9259-69. doi:10.1128/ JVI.00888-06
175. Vetter ML, Johnson ME, Antons AK, Unutmaz D,D'Aquila RT. Differences inAPOBEC3G expression in CD4+Thelperlymphocytesub-types modulate HIV-1 infectivity. PLoS Pathog (2009) 5:e1000292. doi:10.1371/journal.ppat.1000292
176. Smith HC. APOBEC3G: a double agent in defense. Trends Biochem Sci (2011) 36:239-44. doi:10.1016/ j.tibs.2010.12.003
177. Simon V, Zennou V, Murray D, HuangY,HoDD,BieniaszPD. Natural variation in Vif: differential impact on APOBEC3G/3F and a potential role in HIV-1 diversification. PLoS Pathog (2005) 1:e6. doi:10.1371/journal.ppat.0010006
178. An P, Bleiber G, Duggal P, Nelson G, May M, Mangeat B, et al. APOBEC3G genetic variants and their influence on the progression to AIDS. J Virol (2004) 78:11070-6. doi:10.1128/ JVI.78.20.11070-11076.2004
179. Jin X, Brooks A, Chen H, Bennett R, Reichman R, Smith H. APOBEC3G/CEM15(hA3G) mRNA levels associate inversely with human immunodeficiency virus viremia. J Virol (2005) 79:11513-6. doi:10.1128/JVI.79. 17.11513-11516.2005
180. JinX,Wu H,SmithH.APOBEC3G levels predict rates of progression to AIDS. Retrovirology (2007) 4:20. doi:10.1186/1742-4690-4-20
181. Reddy K, Winkler CA, Werner L, Mlisana K, Abdool Karim SS, Ndung'u T. APOBEC3G expression is dysregulated in primary HIV-1 infection and polymorphic variants influence CD4+ T-cell counts andplasma viralload.AIDS (2010) 24:195-204. doi:10.1097/ QAD.0b013e3283353bba
182. Vazquez-Perez JA, Ormsby CE, Hernandez-Juan R, Torres KJ, Reyes-Teran G. APOBEC3G mRNA expression in exposed seronegative and early stage HIV infected individuals decreases with removal of exposure and with disease progression. Retrovirology (2009) 6:23. doi:10.1186/1742-4690-6-23
183. Do H,Vasilescu A, Diop G, Hirtzig T, Heath SC, Coulonges C, et al. Exhaustive genotyping of the CEM15 (APOBEC3G) gene and absence of association with AIDS progression in a French cohort. J Infect Dis (2005) 191:159-63. doi: 10.1086/426826
184. Cho SJ, Drechsler H, Burke RC, Arens MQ, Powderly W, Davidson NO. APOBEC3F and APOBEC3G mRNA levels do not correlate with human immunodeficiency virus type 1 plasma viremia or CD4+ T-cell count. J Virol (2006) 80:2069-72. doi:10.1128/JVI.80.4. 2069-2072.2006
185. Ulenga NK, Sarr AD, Thakore-Meloni S, Sankale JL, Eisen G, Kanki PJ. Relationship between human immunodeficiency type 1 infection and expressionof human APOBEC3G and APOBEC3F. J Infect Dis (2008) 198:486-92. doi: 10.1086/590212
186. Zhao M, Geng W, Jiang Y, Han X, Cui H, Dai D, et al. The associations of hA3G and hA3B mRNA levels with HIV disease progression among HIV-infected individuals of China. J Acquir Immune Defic Syndr (2010) 53(Suppl 1):S4-9. doi:10.1097/ QAI.0b013e3181c7d349
187. Gandhi SK, Siliciano JD, Bailey JR, Siliciano RF, Blankson JN. Role of APOBEC3G/F-mediated hypermutation in the control of human immunodeficiency virus type 1 in elite suppressors. J Virol (2008) 82:3125-30. doi:10.1128/ JVI.01533-07
188. Land AM, Ball TB, Luo M, Pilon R, Sandstrom P, Embree JE, et al. Human immunodeficiency virus (HIV) type 1 proviral hypermuta-tion correlates with CD4 count in HIV-infected women from Kenya. J Virol (2008) 82:8172-82. doi:10. 1128/JVI.01115-08
189. Piantadosi A, Humes D, Chohan B, McClelland RS, Overbaugh J. Analysis of the percentage of human immunodeficiency virus type 1 sequences that are hyper-mutated and markers of disease progression in a longitudinal cohort, including one individual with a partially defective Vif. J Virol (2009) 83:7805-14. doi:10. 1128/JVI.00280-09
190. Buzon MJ, Seiss K, Weiss R, Brass AL, Rosenberg ES, Pereyra F, et al. Inhibition of HIV-1 integration in ex vivo-infected CD4 T cells from elite controllers. J Virol (2011) 85:9646-50. doi:10.1128/ JVI.05327-11
191. Graf EH, Mexas AM, Yu JJ, Sha-heenF,Liszewski MK,DiMM,etal. Elite suppressors harbor low levels of integrated HIV DNA and high levels of 2-LTR circular HIV DNA compared to HIV+ patients on and off HAART. PLoS Pathog (2011) 7:e1001300. doi:10.1371/ journal.ppat.1001300
192. Kourteva Y, De PM, Allos T, McMunn C, D'Aquila RT. APOBEC3Gexpressionand hyper-mutation are inversely associated with human immunodeficiency virus type 1 (HIV-1) burden in vivo. Virology (2012) 430:1-9. doi:10.1016/j.virol.2012.03.018
193. Pido-Lopez J, Whittall T, Wang Y, Bergmeier LA, Babaahmady K, Singh M, et al. Stimulation of cell surface CCR5 and CD40 molecules by their ligands or by HSP70 up-regulates APOBEC3G expression in CD4(+) T cells and dendritic cells. J Immunol (2007) 178:1671-9.
194. Lafferty MK, Sun L, DeMasi L, Lu W, Garzino-Demo A. CCR6 ligands inhibit HIV by inducing APOBEC3G. Blood (2010) 115:1564-71. doi:10.1182/blood-2009-06-226423
195. Ali A, Wang J, Nathans RS, Cao H, SharovaN,StevensonM,etal. Synthesis and structure-activity relationship studies of HIV-1 virion infectivity factor (Vif) inhibitors that block viral replication. ChemMedChem(2012)7:1217-29. doi:10.1002/cmdc.201200079
196. Nathans R, Cao H, Sharova N, Ali A, Sharkey M, Stranska R, et al. Small-molecule inhibition of HIV-1 Vif. Nat Biotechnol (2008) 26:1187-92. doi:10.1038/nbt.1496
197. Goncalves J, Silva F, Freitas-Vieira A, Santa-Marta M, Malho R, Yang X, et al. Functional neutralization of HIV-1 Vif protein by intracellu-lar immunization inhibits reverse transcription and viral replication. J Biol Chem (2002) 277: 32036-45.doi:10.1074/jbc. M201906200
198. Cen S, Peng ZG, Li XY, Li ZR, Ma J, Wang YM, et al. Small molecular compounds inhibit HIV-1 replication through specifically stabilizing APOBEC3G. J Biol Chem (2010) 285:16546-52. doi: 10.1074/jbc.M109.085308
199. Ao Z, Yu Z, Wang L, Zheng Y, Yao X.Vpr14-88-Apobec3G fusion protein is efficiently incorporated into Vif-positive HIV-1 particles and inhibits viral infection. PLoS ONE (2008) 3:e1995. doi:10.1371/ journal.pone.0001995
200. Green LA, Liu Y, He JJ. Inhibition of HIV-1 infection and replication by enhancing viral incorporation of innate anti-HIV-1 protein A3G: a non-pathogenic Nef mutant-based anti-HIV strategy. J Biol Chem (2009) 284:13363-72. doi:10.1074/jbc.M806631200
201. Porcellini S, Gubinelli F, Alberici L, Piovani BM, Rizzardi GP, Bov-olenta C. Chim3 confers survival advantage to CD4+ T cells upon HIV-1 infection by preventing HIV-1 DNA integration and HIV-1-induced G2 cell-cycle delay. Blood (2010) 115:4021-9. doi:10.1182/blood-2009-09-243030
202. Reymond A, Meroni G, Fantozzi A, Merla G, Cairo S, Luzi L, et al. The tripartite motif family identifies cell compartments. EMBO J (2001) 20:2140-51. doi:10.1093/ emboj/20.9.2140
203. Meroni G, Diez-Roux G. TRIM/RBCC, a novel class of 'single protein RING finger' E3 ubiquitin ligases. Bioessays (2005) 27:1147-57. doi:10.1002/bies.20304
204. Ozato K, Shin DM, Chang TH, Morse HC III. TRIM family proteins and their emerging roles in innate immunity. Nat Rev Immunol (2008) 8:849-60. doi:10. 1038/nri2413
205. Nisole S, Stoye JP, Saib A. TRIM family proteins: retroviral restriction and antiviral defence. Nat Rev Microbiol (2005) 3:799-808. doi: 10.1038/nrmicro1248
206. Sayah DM, Sokolskaja E,Berthoux L, Luban J. Cyclophilin A retro-transposition into TRIM5 explains owl monkey resistance to HIV-1. Nature (2004) 430:569-73. doi:10. 1038/nature02777
207. Stremlau M, Owens CM, Perron MJ, Kiessling M, Autissier P, Sodroski J. The cytoplasmic body component TRIM5alpha restricts HIV-1 infection inold world monkeys. Nature (2004) 427:848-53. doi:10.1038/nature02343
208. Perron MJ, Stremlau M, Song B, Ulm W, Mulligan RC, Sodroski J. TRIM5alpha mediates the pos-tentry block to N-tropic murine leukemia viruses in human cells. Proc Natl Acad Sci U S A (2004) 101:11827-32. doi:10.1073/pnas. 0403364101
209. Yap MW, Nisole S, Lynch C, Stoye JP. Trim5alpha protein restricts both HIV-1 and murine leukemia virus. Proc Natl Acad Sci U S A (2004) 101:10786-91. doi:10. 1073/pnas.0402876101
210. Nisole S, Lynch C, Stoye JP, Yap MW.A Trim5-cyclophilinA fusion protein found in owl monkey kidney cells can restrict HIV-1. Proc Natl Acad Sci U S A (2004) 101:13324-8. doi:10.1073/ pnas.0404640101
211. Perez-Caballero D, Hatziioannou T, Yang A, Cowan S, Bieniasz PD. Human tripartite motif 5alpha domains responsible for retrovirus restriction activity and specificity. J Virol (2005) 79:8969-78. doi:10. 1128/JVI.79.14.8969-8978.2005
212. Stremlau M, Perron M, Welikala S, Sodroski J. Species-specific variation in the B30.2(SPRY) domain of TRIM5alpha determines the potency of human immunodeficiency virus restriction. J Virol (2005) 79:3139-45. doi:10.1128/JVI.79.5.3139-3145. 2005
213. Diaz-Griffero F, Qin XR, Hayashi F, Kigawa T, Finzi A, Sarnak Z, et al. A B-box 2 surface patch important for TRIM5alpha self-association, capsid binding avidity, and retrovirus restriction. J Virol (2009) 83:10737-51. doi:10.1128/ JVI.01307-09
214. Kar AK, Diaz-Griffero F, Li Y, Li X, Sodroski J. Biochemical and biophysical characterization of a chimeric TRIM21-TRIM5alpha protein. J Virol (2008) 82:11669-81. doi:10.1128/JVI.01559-08
215. Langelier CR, Sandrin V, Eck-ert DM, Christensen DE, Chan-drasekaran V, Alam SL, et al. Biochemical characterization of a recombinant TRIM5alpha protein that restricts human immunodeficiency virus type 1 replication. J Virol (2008) 82:11682-94. doi:10. 1128/JVI.01562-08
216. Ganser-Pornillos BK, Chan-drasekaranV,PornillosO,Sodroski JG, Sundquist WI, Yeager M. Hexagonal assembly of a restricting TRIM5alpha protein. Proc Natl Acad Sci U S A (2011) 108:534-9. doi:10.1073/pnas.1013426108
217. Javanbakht H, Yuan W, Yeung DF, Song B, Diaz-Griffero F, Li Y, et al. Characterization of TRIM5alpha trimerization and its contribution to human immunodeficiency virus capsid binding. Virology (2006) 353:234-46. doi:10.1016/j. virol.2006.05.017
218. Li X, Sodroski J. The TRIM5alpha B-box 2 domain promotes cooperative binding to the retrovi-ral capsid by mediating higher-order self-association. J Virol (2008)82:11495-502. doi:10.1128/ JVI.01548-08
219. Mische CC, Javanbakht H, Song B, Diaz-Griffero F, Stremlau M, Strack B, et al. Retroviral restriction factor TRIM5alpha is a trimer. J Virol (2005) 79:14446-50. doi:10.1128/JVI.79.22.14446-14450.2005
220. Pertel T, Hausmann S, Morger D, Zuger S, Guerra J, Lascano J, et al. TRIM5 is an innate immune sensor for the retrovirus capsid lattice. Nature (2011) 472:361-5. doi:10. 1038/nature09976
221. Javanbakht H, Diaz-Griffero F, Stremlau M, Si Z, Sodroski J. The contribution of RING and B-box 2 domains to retroviral restriction mediatedbymonkeyTRIM5alpha. J Biol Chem (2005) 280:26933-40. doi:10.1074/jbc.M502145200
222. Stremlau M, Perron M, Lee M, Li Y, Song B, Javanbakht H, et al. Specific recognition and accelerated uncoating of retroviral cap-sids by the TRIM5alpha restriction factor. Proc Natl Acad Sci U S A (2006) 103:5514-9. doi:10.1073/ pnas.0509996103
223. Wu X, Anderson JL, Campbell EM, Joseph AM, Hope TJ. Protea-some inhibitors uncouple rhesus TRIM5alpha restriction of HIV-1 reverse transcription and infection. Proc Natl Acad Sci U S A (2006) 103:7465-70. doi:10.1073/ pnas.0510483103
224. Goldschmidt V, Bleiber G, May M, Martinez R, Ortiz M, Telenti A,Role of common human TRIM5alpha variants in HIV-1 disease progression. Retrovi-rology (2006) 3:54. doi:10.1186/1742-4690-3-S1-S54
225. Sawyer SL,Wu LI, Akey JM, Emer-manM,Malik HS. High-frequency persistence of an impaired allele of the retroviral defense gene TRIM5alpha in humans. Curr Biol (2006) 16:95-100. doi:10.1016/j. cub.2005.11.045
226. Javanbakht H, An P, Gold B,Petersen DC, O'Huigin C, Nelson GW, et al. Effects of human TRIM5alpha polymorphisms on antiretroviral function and susceptibility to human immunodeficiency virus infection. Virology (2006) 354:15-27. doi:10.1016/j.virol.2006.06.031
227. Nakayama EE, Carpentier W, Costagliola D, Shioda T, Iwamoto A, Debre P, et al. Wild type and H43Y variant of human TRIM5alpha show similar anti-human immunodeficiency virus type 1 activity both in vivo and in vitro. Immunogenetics (2007) 59:511-5. doi:10.1007/s00251-007-0217-7
228. Liu FL, Qiu YQ, Li H, Kuang YQ, Tang X, Cao G, et al. An HIV-1 resistance polymor-phisminTRIM5alpha gene among Chinese intravenous drug users. J Acquir Immune Defic Syndr (2011) 56:306-11. doi:10.1097/ QAI.0b013e318205a59b
229. Price H, Lacap P, Tuff J, Wachihi C,Kimani J, Ball TB, et al. A TRIM5alpha exon 2 polymor phism is associated with protection from HIV-1 infection in the Pumwani sex worker cohort. AIDS (2010) 24:1813-21. doi:10.1097/ QAD.0b013e32833b5256
230. van Manen D, Rits MA, Beugeling C, van Dort K, Schuitemaker H, Kootstra NA. The effect of Trim5 polymorphisms on the clinical course of HIV-1 infection. PLoS Pathog (2008) 4:e18. doi:10.1371/journal.ppat. 0040018
231. Anderson J, Akkina R. TRIM5alpharhexpression restricts HIV-1 infection in lentiviral vector-transduced CD34+-cell-derived macrophages. Mol Ther (2005) 12:687-96. doi:10.1016/j.ymthe.2005.07.291
232. Anderson J, Akkina R. Human immunodeficiency virus type 1 restriction by human-rhesus chimeric tripartite motif 5alpha (TRIM 5alpha) in CD34(+) cell-derived macrophages in vitro and in T cells in vivo in severe combinedimmunodeficient (SCID-hu) mice transplanted with human fetal tissue. Hum Gene Ther (2008) 19:217-28. doi:10.1089/hum.2007.108
233. Anderson JS, Javien J, Nolta JA, Bauer G. Preintegration HIV-1 inhibition by a combination lentiviral vector containing a chimeric TRIM5 alpha protein, a CCR5 shRNA, and a TAR decoy. Mol Ther (2009) 17:2103-14. doi: 10.1038/mt.2009.187
234. Walker JE, Chen RX, McGee J, NaceyC,PollardRB,AbediM,etal. Generation of an HIV-1-resistant immune system with CD34(+) hematopoietic stem cells transduced with a triple-combination anti-HIV lentiviral vector. J Virol (2012) 86:5719-29. doi:10.1128/ JVI.06300-11
235. Neagu MR, Ziegler P, Pertel T, Strambio-De-Castillia C, Grutter C, Martinetti G, et al. Potent inhibition of HIV-1 by TRIM5-cyclophilin fusion proteins engineered from human components. J Clin Invest (2009) 119:3035-47. doi:10.1172/JCI39354
236. Pham QT, Bouchard A, Grutter MG, Berthoux L. Generation of human TRIM5alpha mutants with high HIV-1 restriction activity. Gene Ther (2010) 17:859-71. doi: 10.1038/gt.2010.40
237. Andrew AJ, Kao S, Strebel K. C-terminal hydrophobic region in human bone marrow stromal cell antigen 2 (BST-2)/tetherin protein functions as second transmembrane motif. J Biol Chem (2011) 286:39967-81. doi:10.1074/jbc.M111.287011
238. Kupzig S, Korolchuk V, Rolla-son R, Sugden A, Wilde A, Banting G. Bst-2/HM1.24 is a raft-associated apical membrane protein with an unusual topology. Traffic (2003) 4:694-709. doi:10. 1034/j.1600-0854.2003.00129.x
239. Habermann A, Krijnse-Locker J, Oberwinkler H, Eckhardt M, Homann S, Andrew A, et al. CD317/tetherin is enriched in the HIV-1 envelope and downreg-ulated from the plasma membrane upon virus infection. J Virol (2010) 84:4646-58. doi:10.1128/ JVI.02421-09
240. Masuyama N, Kuronita T, Tanaka R, Muto T, Hirota Y, Takigawa A, et al. HM1.24 is internalized from lipid rafts by clathrin-mediated endocytosis through interaction with alpha-adaptin. J Biol Chem (2009) 284:15927-41. doi:10.1074/jbc.M109.005124
241. Rollason R, Korolchuk V, Hamilton C,Schu P,Banting G. Clathrin-mediated endocytosis of a lipid-raft-associated protein is mediated through a dual tyrosine motif. J Cell Sci (2007) 120:3850-8. doi:10. 1242/jcs.003343
242. Ohtomo T, Sugamata Y, Ozaki Y, Ono K,YoshimuraY,Kawai S,et al. Molecular cloning and characterization of a surface antigen preferentially overexpressed on multiple myeloma cells. Biochem Biophys Res Commun (1999) 258:583-91. doi:10.1006/bbrc.1999.0683
243. Schubert HL, Zhai Q, Sandrin V, Eckert DM, Garcia-Maya M, Saul L, et al. Structural and functional studies on the extracellular domain of BST2/tetherin in reduced and oxidized conformations. Proc Natl Acad Sci U S A (2010) 107:17951-6. doi:10.1073/ pnas.1008206107
244. Yang H, Wang J, Jia X, McNatt MW, Zang T, Pan B, et al. Structural insight into the mechanisms of enveloped virus tethering by tetherin. Proc Natl Acad Sci U S A (2010) 107:18428-32. doi:10. 1073/pnas.1011485107
245. Hinz A, Miguet N, Natrajan G, UsamiY,YamanakaH,RenestoP,et al. Structural basis of HIV-1 tethering to membranes by the BST-2/tetherin ectodomain. Cell Host Microbe (2010) 7:314-23. doi:10. 1016/j.chom.2010.03.005
246. Ishikawa J, Kaisho T, Tomizawa H, Lee BO, Kobune Y, Inazawa J, et al. Molecular cloning and chromosomal mapping of a bone marrow stromal cell surface gene, BST2, that may be involved in pre-B-cell growth. Genomics (1995) 26:527-34. doi:10.1016/ 0888-7543(95)80171-H
247. Blasius AL, Giurisato E, Cella M, Schreiber RD, Shaw AS, Colonna M. Bone marrow stromal cell antigen 2 is a specific marker of type I IFN-producing cells in the naïve mouse, but a promiscuous cell surface antigen following IFNstimulation.J Immunol (2006) 177:3260-5.
248. Miyagi E, Andrew AJ, Kao S, Strebel K. Vpu enhances HIV-1 virus release in the absence of Bst-2 cell surface down-modulation and intracellular depletion. Proc Natl Acad Sci U S A (2009) 106:2868-73. doi:10.1073/pnas.0813223106
249. Vidal-LalienaM,RomeroX,March S, Requena V, Petriz J, Engel P. Characterization of antibodies submitted to the B cell section of the 8th human leukocyte differentiation antigens workshop by flow cytometry and immunohis-tochemistry. Cell Immunol (2005) 236:6-16. doi:10.1016/j.cellimm. 2005.08.002
250. Cao W, Bover L, Cho M, Wen X, Hanabuchi S, Bao M, et al. Regulation of TLR7/9 responses in plas-macytoid dendritic cells by BST2 and ILT7 receptor interaction. J Exp Med (2009) 206:1603-14. doi: 10.1084/jem.20090547
251. Neil SJ, Zang T, Bieniasz PD. Teth-erin inhibits retrovirus release and is antagonized by HIV-1 Vpu. Nature (2008) 451:425-30. doi:10. 1038/nature06553
252. Van Damme N, Goff D, Katsura C, Jorgenson RL, Mitchell R, Johnson MC, et al. The interferon-induced protein BST-2 restricts HIV-1 release and is downreg-ulated from the cell surface by the viral Vpu protein. Cell Host Microbe (2008) 3:245-52. doi:10. 1016/j.chom.2008.03.001
253. Swiecki M, Wang Y, Gilfillan S, Lenschow DJ, Colonna M. Cutting edge: paradoxical roles of BST2/tetherin in promoting type I IFN response and viral infection. J Immunol (2012) 188:2488-92. doi: 10.4049/jimmunol.1103145
254. Miyakawa K, Ryo A, Murakami T, Ohba K, Yamaoka S, Fukuda M, et al. BCA2/Rabring7 promotes tetherin-dependent HIV-1 restriction. PLoS Pathog (2009) 5:e1000700. doi:10.1371/journal. ppat.1000700
255. Casartelli N, Sourisseau M, Feld-mann J, Guivel-Benhassine F, Mallet A, Marcelin AG, et al. Tetherin restricts productive HIV-1 cell-to-cell transmission. PLoS Pathog (2010) 6:e1000955. doi:10. 1371/journal.ppat.1000955
256. Jolly C, Booth NJ, Neil SJ. Cell-cell spread of human immunodeficiency virus type 1 overcomes tetherin/BST-2-mediated restriction in T cells. J Virol (2010) 84:12185-99. doi:10.1128/JVI.01447-10
257. Kuhl BD, Sloan RD, Donahue DA, Bar-Magen T, Liang C, Wainberg MA. Tetherin restricts direct cell-to-cell infection of HIV-1. Retrovi-rology (2010) 7:115. doi:10.1186/ 1742-4690-7-115
258. Liberatore RA, Bieniasz PD. Teth-erin is a key effector of the anti-retroviral activity of type I inter-feron in vitro and in vivo. Proc Natl Acad Sci U S A (2011) 108:18097-101. doi:10.1073/pnas. 1113694108
259. Fitzpatrick K, Skasko M, Deer-inck TJ, Crum J, Ellisman MH, Guatelli J. Direct restriction of virus release and incorporation of the interferon-induced protein BST-2 into HIV-1 particles. PLoS Pathog (2010) 6:e1000701. doi:10. 1371/journal.ppat.1000701
260. HammondsJ,Wang JJ,YiH,Spear-man P. Immunoelectron microscopic evidence for Tetherin/BST2 as the physical bridge between HIV-1 virions and the plasma membrane. PLoS Pathog (2010) 6:e1000749. doi:10.1371/journal. ppat.1000749
261. Perez-Caballero D, Zang T, Ebrahimi A, McNatt MW, Gregory DA, Johnson MC, et al. Tetherin inhibits HIV-1 release by directly tethering virions to cells. Cell (2009) 139:499-511. doi:10.1016/j.cell.2009.08.039
262. Kuhl BD, Cheng V, Wainberg MA, Liang C. Tetherin and its viral antagonists. J Neuroimmune Pharmacol (2011) 6:188-201. doi:10. 1007/s11481-010-9256-1
263. Douglas JL, Viswanathan K, McCarroll MN, Gustin JK, Fruh K, Moses AV. Vpu directs the degradation of the human immunodeficiency virus restriction factor BST-2/Tetherin via a [beta]TrCP-dependent mechanism. J Virol (2009) 83:7931-47. doi:10.1128/JVI.00242-09
264. Dube M, Roy BB, Guiot-Guillain P, Binette J, Mercier J, Chiasson A, et al. Antagonism of tetherin restriction of HIV-1 release byVpu involves binding and sequestration of the restriction factor in a perinuclear compartment. PLoS Pathog (2010) 6:e1000856. doi:10. 1371/journal.ppat.1000856
265. GoffinetC,Allespach I,Homann S, Tervo HM, HabermannA,Rupp D, et al. HIV-1 antagonism of CD317 is species specific and involves Vpu-mediated proteasomal degradation of the restriction factor. Cell Host Microbe (2009) 5:285-97. doi: 10.1016/j.chom.2009.01.009
266. Iwabu Y, Fujita H, Kinomoto M, Kaneko K, Ishizaka Y, Tanaka Y, et al. HIV-1 accessory protein Vpu internalizes cell-surface BST-2/tetherin through transmembraneinteractions leading to lysosomes. J Biol Chem (2009) 284:35060-72. doi:10.1074/jbc.M109.058305
267. Mitchell RS, Katsura C, Skasko MA, Fitzpatrick K, Lau D, Ruiz A, et al. Vpu antagonizes BST-2-mediated restriction of HIV-1 release via beta-TrCP and endo-lysosomal trafficking. PLoS Pathog (2009) 5:e1000450. doi:10.1371/journal.ppat.1000450
268. Skasko M,WangY,Tian Y,Tokarev A, Munguia J, Ruiz A, et al. HIV-1 Vpu protein antagonizes innate restriction factor BST-2 via lipid-embedded helix-helix interactions. J Biol Chem (2012) 287:58-67. doi: 10.1074/jbc.M111.296772
269. Hauser H, Lopez LA, Yang SJ, Oldenburg JE, Exline CM, Guatelli JC, et al. HIV-1 Vpu and HIV-2 Env counteract BST-2/tetherin by sequestration in a perinu-clear compartment. Retrovirology (2010) 7:51. doi:10.1186/1742-4690-7-51
270. Le Tortorec A, Neil SJ. Antagonism to and intracellular sequestration of human tetherin by the human immunodeficiency virus type 2 envelope glycoprotein. J Virol (2009) 83:11966-78. doi:10. 1128/JVI.01515-09
271. Mous K, Jennes W, Camara M, Seydi M, Daneau G, Mboup S, et al. Expression analysis of LEDGF/p75, APOBEC3G, TRIM5alpha, and tetherin in a Senegalese cohort of HIV-1-exposed seronegative individuals. PLoS ONE (2012) 7:e33934. doi: 10.1371/journal.pone.0033934
272. Homann S,Smith D,Little S,Rich-man D, Guatelli J. Upregulation of BST-2/Tetherin by HIV infection in vivo.J Virol (2011) 85:10659-68. doi:10.1128/JVI.05524-11
273. Pillai SK, Abdel-Mohsen M, Guatelli J, Skasko M, Monto A, Fujimoto K, et al. Role of retroviral restriction factors intheinterferon-alpha-mediated suppression of HIV-1 in vivo. Proc Natl Acad Sci U S A (2012) 109:3035-40. doi:10.1073/pnas.1111573109
274. Herbeuval JP, Shearer GM. HIV-1 immunopathogenesis: how good interferonturns bad.ClinImmunol (2007) 123:121-8. doi:10.1016/j. clim.2006.09.016
275. Lv M, Wang J, Zhu Y, Wang X, Zuo T, Liu D, et al. Over-expression of inactive tetherin delGPI mutant inhibits HIV-1 Vpu-mediated antagonism of endogenous tetherin. FEBS Lett (2013) 587:37-43. doi:10.1016/j. febslet.2012.11.022
276. Aviv T, Lin Z, Lau S, Rendl LM, Sicheri F, Smibert CA. The RNA-binding SAM domain of Smaug defines a new family of post-transcriptional regulators. Nat Struct Biol (2003) 10:614-21. doi:10.1038/nsb956
277. Oberstrass FC, Lee A, Stefl R, Janis M, Chanfreau G, Allain FH. Shape-specific recognition in the structure of the Vts1p SAM domain with RNA. Nat Struct Mol Biol (2006) 13:160-7. doi:10.1038/ nsmb1038
278. Brandariz-Nunez A, Valle-Casuso JC, White TE, Laguette N, Benki-rane M, Brojatsch J, et al. Role of SAMHD1 nuclear localization in restriction of HIV-1 and SIVmac. Retrovirology (2012) 9:49. doi:10. 1186/1742-4690-9-49
279. Hofmann H, Logue EC, Bloch N, Daddacha W, Polsky SB, Schultz ML, et al. The Vpx lentiviral accessory protein targets SAMHD1 for degradation in the nucleus. J Virol (2012) 86:12552-60. doi:10.1128/JVI.01657-12
280. White TE, Brandariz-Nunez A, Carlos Valle-Casuso J, Amie S, Nguyen L, Kim B, et al. Contri bution of SAM and HD domains to retroviral restriction mediated by human SAMHD1. Virology (2013)436:81-90. doi:10.1016/j.virol.2012.10.029
281. Baldauf HM, Pan X, Erikson E, Schmidt S, Daddacha W, Burggraf M, et al. SAMHD1 restricts HIV-1 infection in resting CD4(+) T cells. Nat Med (2012) 18:1682-7. doi:10.1038/nm.2964
282. Wu L. SAMHD1: a new contributor to HIV-1 restriction in resting CD4+ T-cells. Retrovirology (2012) 9:88. doi:10.1186/1742-4690-9-88
283. Aravind L, Koonin EV. The HD domain defines a new superfam-ily of metal-dependent phospho-hydrolases. Trends Biochem Sci (1998) 23:469-72. doi:10.1016/ S0968-0004(98)01293-6
284. Goldstone DC, Ennis-Adeniran V, Hedden JJ, Groom HC, Rice GI, Christodoulou E, et al. HIV-1 restriction factor SAMHD1 is a deoxynucleoside triphosphate triphosphohydro-lase. Nature (2011) 480:379-82. doi:10.1038/nature10623
285. Berger A, Sommer AF, Zwarg J, Hamdorf M,WelzelK,Esly N,etal. SAMHD1-deficient CD14+ cells from individuals with Aicardi-Goutieres syndrome are highly susceptible to HIV-1 infection. PLoS Pathog (2011) 7:e1002425. doi:10.1371/journal.ppat.1002425
286. St GC, de SS, Amie SM, Coleman CM, Hoy H, Hollenbaugh JA, et al. SAMHD1 restricts HIV-1 infection in dendritic cells (DCs) by dNTP depletion, but its expression in DCs and primary CD4+ T-lymphocytes cannot be upregu-lated by interferons. Retrovirology (2012) 9:105. doi:10.1186/1742-4690-9-105
287. Powell RD, Holland PJ, Hollis T, Perrino FW. Aicardi-Goutieres syndrome gene and HIV-1 restriction factor SAMHD1 is a dGTP-regulated deoxynucleotide triphosphohydrolase. J Biol Chem (2011) 286:43596-600. doi:10.1074/jbc.C111.317628
288. Descours B, Cribier A, Chable-Bessia C, Ayinde D, Rice G, Crow Y, et al. SAMHD1 restricts HIV-1 reverse transcription in quiescent CD4(+) T-cells. Retrovi-rology (2012) 9:87. doi:10.1186/ 1742-4690-9-87
289. Hrecka K, Hao C, Gierszewska M, Swanson SK, Kesik-Brodacka M, Srivastava S, et al. Vpx relieves inhibition of HIV-1 infection of macrophages mediated by the SAMHD1 protein. Nature (2011) 474:658-61. doi:10.1038/ nature10195
290. Laguette N, Sobhian B, Casartelli N, Ringeard M, Chable-Bessia C, Segeral E, et al. SAMHD1 is the dendritic- and myeloid-cell-specific HIV-1 restriction factor counteracted by Vpx. Nature (2011) 474:654-7. doi:10.1038/nature10117\
291. Kim B, Nguyen LA, Daddacha W,Hollenbaugh JA. Tight interplay among SAMHD1 protein level, cellular dNTP levels, and HIV-1 proviral DNA synthesis kinetics in human primary monocyte-derived macrophages. J Biol Chem (2012) 287:21570-4. doi:10.1074/jbc.C112.374843
292. Lahouassa H, Daddacha W, Hofmann H, Ayinde D, LogueEC, Dragin L, et al. SAMHD1 restricts the replication of human immunodeficiency virus type 1 by depleting the intracellular pool of deoxynucleoside triphosphates. Nat Immunol (2012) 13:223-8. doi:10.1038/ni.2236
293. Manel N, Hogstad B, Wang Y, Levy DE, Unutmaz D, Littman DR. A cryptic sensor for HIV-1 activates antiviral innate immunity in dendritic cells. Nature (2010) 467:214-7. doi:10.1038/ nature09337
294. Welbourn S, Miyagi E, White TE, Diaz-Griffero F, Strebel K. Identification and characterization of naturally occurring splice variants of SAMHD1. Retrovirology (2012) 9:86. doi:10.1186/1742-4690-9-86
295. Rice GI, Bond J, Asipu A, Brunette RL, Manfield IW, Carr IM, et al. Mutations involved in Aicardi-Goutieres syndrome implicate SAMHD1 as regulator of the innate immune response. Nat Genet (2009) 41:829-32. doi:10. 1038/ng.373
296. Coon S, Wang D, Wu L. Polymorphisms of the SAMHD1 gene are not associated with the infection and natural control of HIV type 1 in Europeans and African-Americans. AIDS Res Hum Retro-viruses (2012) 28:1565-73. doi:10. 1089/AID.2012.0039