Impaired Nef function is associated with early control of HIV-1 viremia

Journal of Virology

Volumn 88, Issue 17, 2014, Pages 10200-10213

  Kuang, Xiaomei T ^a   Li, Xiaoguang ^b   Anmole, Gursev ^a   Mwimanzi, Philip ^a   Shahid, Aniqa ^a   Le, Anh Q ^a   Chong, Louise ^a   Qian, Hua ^b   Miura, Toshiyuki ^c   Markle, Tristan ^a,m   Baraki, Bemuluyigza ^a   Connick, Elizabeth ^d   Daar, Eric S ^e   Jessen, Heiko ^f   Kelleher, Anthony D ^g   Little, Susan ^h   Markowitz, Martin ⁱ   Pereyra, Florencia ^c,j,n   Rosenberg, Eric S ^j   Walker, Bruce D ^c,j,k   Ueno, Takamasa ^b   Brumme, Zabrina L ^a,l   Brockman, Mark A ^a,l   more..

^a SIMON FRASER UNIVERSITY   (Canada)

^b KUMAMOTO UNIVERSITY   (Japan)

^c MASSACHUSETTS INSTITUTE OF TECHNOLOGY   (United States)

^d UNIVERSITY OF COLORADO   (United States)

^e UNIVERSITY OF CALIFORNIA   (United States)

^f Jessen Praxis   (Germany)

^g UNIVERSITY OF NEW SOUTH WALES   (Australia)

^h UNIVERSITY OF CALIFORNIA   (United States)

ⁱ AARON DIAMOND AIDS RESEARCH CENTER   (United States)

^j MASSACHUSETTS GENERAL HOSPITAL   (United States)

^k HOWARD HUGHES MEDICAL INSTITUTE   (United States)

^l BRITISH COLUMBIA CENTRE FOR EXCELLENCE IN HIV AIDS   (Canada)

^m VIIV HEALTHCARE   (United States)

ⁿ NOVARTIS INSTITUTES FOR BIOMEDICAL RESEARCH   (United States)

more..

Author keywords

[No Author keywords available]

Indexed keywords

CD4 ANTIGEN; HLA ANTIGEN CLASS 1; NEF PROTEIN; NEF PROTEIN, HUMAN IMMUNODEFICIENCY VIRUS 1; VIRUS RNA;

DEFICIENCY; DNA SEQUENCE; DOWN REGULATION; GENETIC POLYMORPHISM; GENETICS; GENOTYPE; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; IMMUNOLOGY; ISOLATION AND PURIFICATION; MOLECULAR GENETICS; PLASMA; VIREMIA; VIROLOGY; VIRUS LOAD;

ANTIGENS, CD4; DOWN-REGULATION; GENOTYPE; HISTOCOMPATIBILITY ANTIGENS CLASS I; HIV INFECTIONS; HIV-1; HUMANS; MOLECULAR SEQUENCE DATA; NEF GENE PRODUCTS, HUMAN IMMUNODEFICIENCY VIRUS; PLASMA; POLYMORPHISM, GENETIC; RNA, VIRAL; SEQUENCE ANALYSIS, DNA; VIRAL LOAD; VIREMIA;

EID: 84906864431     PISSN: 0022538X     EISSN: 10985514     Source Type: Journal    
DOI: 10.1128/JVI.01334-14     Document Type: Article

References (82)

1. Kaslow RA, Carrington M, Apple R, Park L, Munoz A, Saah AJ, Goedert JJ, Winkler C, O'Brien SJ, Rinaldo C, Detels R, Blattner W, Phair J, Erlich H, Mann DL. 1996. Influence of combinations of human major histocompatibility complex genes on the course of HIV-1 infection. Nat. Med. 2:405-411. http://dx.doi.org/10.1038/nm0496-405.
2. Gao X, Nelson GW, Karacki P, Martin MP, Phair J, Kaslow R, Goedert JJ, Buchbinder S, Hoots K, Vlahov D, O'Brien SJ, Carrington M. 2001. Effect of a single amino acid change in MHC class I molecules on the rate of progression to AIDS. N. Engl. J. Med. 344:1668-1675. http://dx.doi.org/10.1056/NEJM200105313442203.
3. International HIV Controllers Study, Pereyra F, Jia X, McLaren PJ, Telenti A, de Bakker PI, Walker BD, Ripke S, Brumme CJ, Pulit SL, Carrington M, Kadie CM, Carlson JM, Heckerman D, Graham RR, Plenge RM, Deeks SG, Gianniny L, Crawford G, Sullivan J, Gonzalez E, Davies L, Camargo A, Moore JM, Beattie N, Gupta S, Crenshaw A, Burtt NP, Guiducci C, Gupta N, Gao X, Qi Y, Yuki Y, Piechocka-Trocha A, Cutrell E, Rosenberg R, Moss KL, Lemay P, O'Leary J, Schaefer T, Verma P, Toth I, Block B, Baker B, Rothchild A, Lian J, Proudfoot J, Alvino DM, Vine S, Addo MM, et al. 2010. The major genetic determinants of HIV-1 control affect HLA class I peptide presentation. Science 330:1551-1557. http://dx.doi.org/10.1126/science.1195271.
4. Fellay J, Shianna KV, Ge D, Colombo S, Ledergerber B, Weale M, Zhang K, Gumbs C, Castagna A, Cossarizza A, Cozzi-Lepri A, De Luca A, Easterbrook P, Francioli P, Mallal S, Martinez-Picado J, Miro JM, Obel N, Smith JP, Wyniger J, Descombes P, Antonarakis SE, Letvin NL, McMichael AJ, Haynes BF, Telenti A, Goldstein DB. 2007. A wholegenome association study of major determinants for host control of HIV-1. Science 317:944-947. http://dx.doi.org/10.1126/science.1143767.
5. McLaren PJ, Coulonges C, Ripke S, van den Berg L, Buchbinder S, Carrington M, Cossarizza A, Dalmau J, Deeks SG, Delaneau O, De Luca A, Goedert JJ, Haas D, Herbeck JT, Kathiresan S, Kirk GD, Lambotte O, Luo M, Mallal S, van Manen D, Martinez-Picado J, Meyer L, Miro JM, Mullins JI, Obel N, O'Brien SJ, Pereyra F, Plummer FA, Poli G, Qi Y, Rucart P, Sandhu MS, Shea PR, Schuitemaker H, Theodorou I, Vannberg F, Veldink J, Walker BD, Weintrob A, Winkler CA, Wolinsky S, Telenti A, Goldstein DB, de Bakker PI, Zagury JF, Fellay J. 2013. Association study of common genetic variants and HIV-1 acquisition in 6, 300 infected cases and 7, 200 controls. PLoS Pathog. 9:e1003515. http://dx.doi.org/10.1371/journal.ppat.1003515.
6. Pereyra F, Addo MM, Kaufmann DE, Liu Y, Miura T, Rathod A, Baker B, Trocha A, Rosenberg R, Mackey E, Ueda P, Lu Z, Cohen D, Wrin T, Petropoulos CJ, Rosenberg ES, Walker BD. 2008. Genetic and immunologic heterogeneity among persons who control HIV infection in the absence of therapy. J. Infect. Dis. 197:563-571. http://dx.doi.org/10.1086/526786.
7. Deeks SG, Walker BD. 2007. Human immunodeficiency virus controllers: mechanisms of durable virus control in the absence of antiretroviral therapy. Immunity 27:406-416. http://dx.doi.org/10.1016/j.immuni.2007.08.010.
8. Migueles SA, Connors M. 2010. Long-term nonprogressive disease among untreated HIV-infected individuals: clinical implications of understanding immune control of HIV. JAMA 304:194-201. http://dx.doi.org/10.1001/jama.2010.925.
9. Ndhlovu ZM, Proudfoot J, Cesa K, Alvino DM, McMullen A, Vine S, Stampouloglou E, Piechocka-Trocha A, Walker BD, Pereyra F. 2012. Elite controllers with low to absent effector CD8+ T cell responses maintain highly functional, broadly directed central memory responses. J. Virol. 86:6959-6969. http://dx.doi.org/10.1128/JVI.00531-12.
10. Hersperger AR, Pereyra F, Nason M, Demers K, Sheth P, Shin LY, Kovacs CM, Rodriguez B, Sieg SF, Teixeira-Johnson L, Gudonis D, Goepfert PA, Lederman MM, Frank I, Makedonas G, Kaul R, Walker BD, Betts MR. 2010. Perforin expression directly ex vivo by HIV-specific CD8 T-cells is a correlate of HIV elite control. PLoS Pathog. 6:e1000917. http://dx.doi.org/10.1371/journal.ppat.1000917.
11. Migueles SA, Laborico AC, Shupert WL, Sabbaghian MS, Rabin R, Hallahan CW, Van Baarle D, Kostense S, Miedema F, McLaughlin M, Ehler L, Metcalf J, Liu S, Connors M. 2002. HIV-specific CD8+ T cell proliferation is coupled to perforin expression and is maintained in nonprogressors. Nat. Immunol. 3:1061-1068. http://dx.doi.org/10.1038/ni845.
12. Hersperger AR, Migueles SA, Betts MR, Connors M. 2011. Qualitative features of the HIV-specific CD8+T-cell response associated with immunologic control. Curr. Opin. HIV AIDS 6:169-173. http://dx.doi.org/10.1097/COH.0b013e3283454c39.
13. Kiepiela P, Ngumbela K, Thobakgale C, Ramduth D, Honeyborne I, Moodley E, Reddy S, de Pierres C, Mncube Z, Mkhwanazi N, Bishop K, van der Stok M, Nair K, Khan N, Crawford H, Payne R, Leslie A, Prado J, Prendergast A, Frater J, McCarthy N, Brander C, Learn GH, Nickle D, Rousseau C, Coovadia H, Mullins JI, Heckerman D, Walker BD, Goulder P. 2007. CD8+ T-cell responses to different HIV proteins have discordant associations with viral load. Nat. Med. 13:46-53. http://dx.doi.org/10.1038/nm1520.
14. Adland E, Carlson JM, Paioni P, Kloverpris H, Shapiro R, Ogwu A, Riddell L, Luzzi G, Chen F, Balachandran T, Heckerman D, Stryhn A, Edwards A, Ndung'u T, Walker BD, Buus S, Goulder P, Matthews PC. 2013. Nef-specific CD8+ T cell responses contribute to HIV-1 immune control. PLoS One 8:e73117. http://dx.doi.org/10.1371/journal.pone.0073117.
15. Riou C, Burgers WA, Mlisana K, Koup RA, Roederer M, Abdool Karim SS, Williamson C, Gray CM. 2014. Differential impact of magnitude, polyfunctional capacity, and specificity of HIV-specific CD8+ T cell responses on HIV set point. J. Virol. 88:1819-1824. http://dx.doi.org/10.1128/JVI.02968-13.
16. Allen TM, Altfeld M. 2008. Crippling HIV one mutation at a time. J. Exp. Med. 205:1003-1007. http://dx.doi.org/10.1084/jem.20080569.
17. Prince JL, Claiborne DT, Carlson JM, Schaefer M, Yu T, Lahki S, Prentice HA, Yue L, Vishwanathan SA, Kilembe W, Goepfert P, Price MA, Gilmour J, Mulenga J, Farmer P, Derdeyn CA, Tang J, Heckerman D, Kaslow RA, Allen SA, Hunter E. 2012. Role of transmitted Gag CTL polymorphisms in defining replicative capacity and early HIV-1 pathogenesis. PLoS Pathog. 8:e1003041. http://dx.doi.org/10.1371/journal.ppat.1003041.
18. Brumme ZL, Li C, Miura T, Sela J, Rosato PC, Brumme CJ, Markle TJ, Martin E, Block BL, Trocha A, Kadie CM, Allen TM, Pereyra F, Heckerman D, Walker BD, Brockman MA. 2011. Reduced replication capacity of NL4-3 recombinant viruses encoding reverse transcriptase-integrase sequences from HIV-1 elite controllers. J. Acquir. Immune Defic. Syndr. 56: 100-108. http://dx.doi.org/10.1097/QAI.0b013e3181fe9450.
19. Lassen KG, Lobritz MA, Bailey JR, Johnston S, Nguyen S, Lee B, Chou T, Siliciano RF, Markowitz M, Arts EJ. 2009. Elite suppressor-derived HIV-1 envelope glycoproteins exhibit reduced entry efficiency and kinetics. PLoS Pathog. 5:e1000377. http://dx.doi.org/10.1371/journal.ppat.1000377.
20. Miura T, Brockman MA, Brumme ZL, Brumme CJ, Pereyra F, Trocha A, Block BL, Schneidewind A, Allen TM, Heckerman D, Walker BD. 2009. HLA-associated alterations in replication capacity of chimeric NL4-3 viruses carrying gag-protease from elite controllers of human immunodeficiency virus type 1. J. Virol. 83:140-149. http://dx.doi.org/10.1128/JVI.01471-08.
21. Mwimanzi P, Markle TJ, Martin E, Ogata Y, Kuang XT, Tokunaga M, Mahiti M, Pereyra F, Miura T, Walker BD, Brumme ZL, Brockman MA, Ueno T. 2013. Attenuation of multiple Nef functions in HIV-1 elite controllers. Retrovirology 10:1. http://dx.doi.org/10.1186/1742-4690-10-1.
22. Lobritz MA, Lassen KG, Arts EJ. 2011. HIV-1 replicative fitness in elite controllers. Curr. Opin. HIV AIDS 6:214-220. http://dx.doi.org/10.1097/COH.0b013e3283454cf5.
23. Rihn SJ, Wilson SJ, Loman NJ, Alim M, Bakker SE, Bhella D, Gifford RJ, Rixon FJ, Bieniasz PD. 2013. Extreme genetic fragility of the HIV-1 capsid. PLoS Pathog. 9:e1003461. http://dx.doi.org/10.1371/journal.ppat.1003461.
24. Crawford H, Prado JG, Leslie A, Hue S, Honeyborne I, Reddy S, van der Stok M, Mncube Z, Brander C, Rousseau C, Mullins JI, Kaslow R, Goepfert P, Allen S, Hunter E, Mulenga J, Kiepiela P, Walker BD, Goulder PJ. 2007. Compensatory mutation partially restores fitness and delays reversion of escape mutation within the immunodominant HLAB* 5703-restricted Gag epitope in chronic human immunodeficiency virus type 1 infection. J. Virol. 81:8346-8351. http://dx.doi.org/10.1128/JVI.00465-07.
25. Martinez-Picado J, Prado JG, Fry EE, Pfafferott K, Leslie A, Chetty S, Thobakgale C, Honeyborne I, Crawford H, Matthews P, Pillay T, Rousseau C, Mullins JI, Brander C, Walker BD, Stuart DI, Kiepiela P, Goulder P. 2006. Fitness cost of escape mutations in p24 Gag in association with control of human immunodeficiency virus type 1. J. Virol. 80: 3617-3623. http://dx.doi.org/10.1128/JVI.80.7.3617-3623.2006.
26. Brockman MA, Schneidewind A, Lahaie M, Schmidt A, Miura T, Desouza I, Ryvkin F, Derdeyn CA, Allen S, Hunter E, Mulenga J, Goepfert PA, Walker BD, Allen TM. 2007. Escape and compensation from early HLA-B57-mediated cytotoxic T-lymphocyte pressure on human immunodeficiency virus type 1 Gag alter capsid interactions with cyclophilin A. J. Virol. 81:12608-12618. http://dx.doi.org/10.1128/JVI.01369-07.
27. Rolland M, Manocheewa S, Swain JV, Lanxon-Cookson EC, Kim M, Westfall DH, Larsen BB, Gilbert PB, Mullins JI. 2013. HIV-1 conservedelement vaccines: relationship between sequence conservation and replicative capacity. J. Virol. 87:5461-5467. http://dx.doi.org/10.1128/JVI.03033-12.
28. Brockman MA, Brumme ZL, Brumme CJ, Miura T, Sela J, Rosato PC, Kadie CM, Carlson JM, Markle TJ, Streeck H, Kelleher AD, Markowitz M, Jessen H, Rosenberg E, Altfeld M, Harrigan PR, Heckerman D, Walker BD, Allen TM. 2010. Early selection in Gag by protective HLA alleles contributes to reduced HIV-1 replication capacity that may be largely compensated for in chronic infection. J. Virol. 84:11937-11949. http://dx.doi.org/10.1128/JVI.01086-10.
29. Brockman MA, Chopera DR, Olvera A, Brumme CJ, Sela J, Markle TJ, Martin E, Carlson JM, Le AQ, McGovern R, Cheung PK, Kelleher AD, Jessen H, Markowitz M, Rosenberg E, Frahm N, Sanchez J, Mallal S, John M, Harrigan PR, Heckerman D, Brander C, Walker BD, Brumme ZL. 2012. Uncommon pathways of immune escape attenuate HIV-1 integrase replication capacity. J. Virol. 86:6913-6923. http://dx.doi.org/10.1128/JVI.07133-11.
30. Troyer RM, McNevin J, Liu Y, Zhang SC, Krizan RW, Abraha A, Tebit DM, Zhao H, Avila S, Lobritz MA, McElrath MJ, Le Gall S, Mullins JI, Arts EJ. 2009. Variable fitness impact of HIV-1 escape mutations to cytotoxic T lymphocyte (CTL) response. PLoS Pathog. 5:e1000365. http://dx.doi.org/10.1371/journal.ppat.1000365.
31. Miura T, Brumme CJ, Brockman MA, Brumme ZL, Pereyra F, Block BL, Trocha A, John M, Mallal S, Harrigan PR, Walker BD. 2009. HLA-associated viral mutations are common in human immunodeficiency virus type 1 elite controllers. J. Virol. 83:3407-3412. http://dx.doi.org/10.1128/JVI.02459-08.
32. Miura T, Brumme ZL, Brockman MA, Rosato P, Sela J, Brumme CJ, Pereyra F, Kaufmann DE, Trocha A, Block BL, Daar ES, Connick E, Jessen H, Kelleher AD, Rosenberg E, Markowitz M, Schafer K, Vaida F, Iwamoto A, Little S, Walker BD. 2010. Impaired replication capacity of acute/early viruses in persons who become HIV controllers. J. Virol. 84: 7581-7591. http://dx.doi.org/10.1128/JVI.00286-10.
33. Mwimanzi P, Markle TJ, Ueno T, Brockman MA. 2012. Human leukocyte antigen (HLA) class I down-regulation by human immunodeficiency virus type 1 negative factor (HIV-1 Nef): what might we learn from natural sequence variants? Viruses 4:1711-1730. http://dx.doi.org/10.3390/v4091711.
34. Garcia JV, Miller AD. 1991. Serine phosphorylation-independent downregulation of cell-surface CD4 by nef. Nature 350:508-511. http://dx.doi.org/10.1038/350508a0.
35. Schwartz O, Marechal V, Le Gall S, Lemonnier F, Heard JM. 1996. Endocytosis of major histocompatibility complex class I molecules is induced by the HIV-1 Nef protein. Nat. Med. 2:338-342. http://dx.doi.org/10.1038/nm0396-338.
36. Schindler M, Wurfl S, Benaroch P, Greenough TC, Daniels R, Easterbrook P, Brenner M, Munch J, Kirchhoff F. 2003. Down-modulation of mature major histocompatibility complex class II and up-regulation of invariant chain cell surface expression are well-conserved functions of human and simian immunodeficiency virus nef alleles. J. Virol. 77:10548-10556. http://dx.doi.org/10.1128/JVI.77.19.10548-10556.2003.
37. Münch J, Rajan D, Schindler M, Specht A, Rücker E, Novembre FJ, Nerrienet E, Müller-Trutwin MC, Peeters M, Hahn BH, Kirchhoff F. 2007. Nef-mediated enhancement of virion infectivity and stimulation of viral replication are fundamental properties of primate lentiviruses. J. Virol. 81:13852-13864. http://dx.doi.org/10.1128/JVI.00904-07.
38. Miller MD, Warmerdam MT, Gaston I, Greene WC, Feinberg MB. 1994. The human immunodeficiency virus-1 nef gene product: a positive factor for viral infection and replication in primary lymphocytes and macrophages. J. Exp. Med. 179:101-113. http://dx.doi.org/10.1084/jem.179.1.101.
39. Abraham L, Fackler OT. 2012. HIV-1 Nef: a multifaceted modulator of T cell receptor signaling. Cell Commun. Signal. 10:39. http://dx.doi.org/10.1186/1478-811X-10-39.
40. Markle TJ, Philip M, Brockman MA. 2013. HIV-1 Nef and T-cell activation: a history of contradictions. Future Virol. 2013:8. http://dx.doi.org/10.2217/fvl.13.20.
41. Daniel MD, Kirchhoff F, Czajak SC, Sehgal PK, Desrosiers RC. 1992. Protective effects of a live attenuated SIV vaccine with a deletion in the nef gene. Science 258:1938-1941. http://dx.doi.org/10.1126/science.1470917.
42. Deacon NJ, Tsykin A, Solomon A, Smith K, Ludford-Menting M, Hooker DJ, McPhee DA, Greenway AL, Ellett A, Chatfield C, Lawson VA, Crowe S, Maerz A, Sonza S, Learmont J, Sullivan JS, Cunningham A, Dwyer D, Dowton D, Mills J. 1995. Genomic structure of an attenuated quasi species of HIV-1 from a blood transfusion donor and recipients. Science 270:988-991. http://dx.doi.org/10.1126/science.270.5238.988.
43. Kirchhoff F, Greenough TC, Brettler DB, Sullivan JL, Desrosiers RC. 1995. Brief report: absence of intact nef sequences in a long-term survivor with nonprogressive HIV-1 infection. N. Engl. J. Med. 332:228-232. http://dx.doi.org/10.1056/NEJM199501263320405.
44. Zaunders JJ, Geczy AF, Dyer WB, McIntyre LB, Cooley MA, Ashton LJ, Raynes-Greenow CH, Learmont J, Cooper DA, Sullivan JS. 1999. Effect of long-term infection with nef-defective attenuated HIV type 1 on CD4+ and CD8+ T lymphocytes: increased CD45RO+CD4+ T lymphocytes and limited activation of CD8+ T lymphocytes. AIDS Res. Hum. Retroviruses 15:1519-1527. http://dx.doi.org/10.1089/088922299309801.
45. Little SJ, Frost SD, Wong JK, Smith DM, Pond SL, Ignacio CC, Parkin NT, Petropoulos CJ, Richman DD. 2008. Persistence of transmitted drug resistance among subjects with primary human immunodeficiency virus infection. J. Virol. 82:5510-5518. http://dx.doi.org/10.1128/JVI.02579-07.
46. Woods CK, Brumme CJ, Liu TF, Chui CK, Chu AL, Wynhoven B, Hall TA, Trevino C, Shafer RW, Harrigan PR. 2012. Automating HIV drug resistance genotyping with RECall, a freely accessible sequence analysis tool. J. Clin. Microbiol. 50:1936-1942. http://dx.doi.org/10.1128/JCM.06689-11.
47. Pond SL, Frost SD, Muse SV. 2005. HyPhy: hypothesis testing using phylogenies. Bioinformatics 21:676-679. http://dx.doi.org/10.1093/bioinformatics/bti079.
48. Guindon S, Gascuel O. 2003. A simple, fast, and accurate algorithm to estimate large phylogenies by maximum likelihood. Syst. Biol. 52:696-704. http://dx.doi.org/10.1080/10635150390235520.
49. Guindon S, Dufayard JF, Lefort V, Anisimova M, Hordijk W, Gascuel O. 2010. New algorithms and methods to estimate maximum-likelihood phylogenies: assessing the performance of PhyML 3.0. Syst. Biol. 59:307-321. http://dx.doi.org/10.1093/sysbio/syq010.
50. Cotton LA, Abdur Rahman M, Ng C, Le AQ, Milloy MJ, Mo T, Brumme ZL. 2012. HLA class I sequence-based typing using DNA recovered from frozen plasma. J. Immunol. Methods 382:40-47. http://dx.doi.org/10.1016/j.jim.2012.05.003.
51. Ueno T, Motozono C, Dohki S, Mwimanzi P, Rauch S, Fackler OT, Oka S, Takiguchi M. 2008. CTL-mediated selective pressure influences dynamic evolution and pathogenic functions of HIV-1 Nef. J. Immunol. 180:1107-1116. http://dx.doi.org/10.4049/jimmunol.180.2.1107.
52. Mwimanzi P, Hasan Z, Hassan R, Suzu S, Takiguchi M, Ueno T. 2011. Effects of naturally-arising HIV Nef mutations on cytotoxic T lymphocyte recognition and Nef's functionality in primary macrophages. Retrovirology 8:50. http://dx.doi.org/10.1186/1742-4690-8-50.
53. Wei X, Decker JM, Liu H, Zhang Z, Arani RB, Kilby JM, Saag MS, Wu X, Shaw GM, Kappes JC. 2002. Emergence of resistant human immunodeficiency virus type 1 in patients receiving fusion inhibitor (T-20) monotherapy. Antimicrob. Agents Chemother. 46:1896-1905. http://dx.doi.org/10.1128/AAC.46.6.1896-1905.2002.
54. Shugars DC, Smith MS, Glueck DH, Nantermet PV, Seillier-Moiseiwitsch F, Swanstrom R. 1993. Analysis of human immunodeficiency virus type 1 nef gene sequences present in vivo. J. Virol. 67:4639-4650.
55. Ho SN, Hunt HD, Horton RM, Pullen JK, Pease LR. 1989. Site-directed mutagenesis by overlap extension using the polymerase chain reaction. Gene 77:51-59. http://dx.doi.org/10.1016/0378-1119(89)90358-2.
56. Mann JK, Byakwaga H, Kuang XT, Le AQ, Brumme CJ, Mwimanzi P, Omarjee S, Martin E, Lee GQ, Baraki B, Danroth R, McCloskey R, Muzoora C, Bangsberg DR, Hunt PW, Goulder PJ, Walker BD, Harrigan PR, Martin JN, Ndung'u T, Brockman MA, Brumme ZL. 2013. Ability of HIV-1 Nef to downregulate CD4 and HLA class I differs among viral subtypes. Retrovirology 10:100. http://dx.doi.org/10.1186/1742-4690-10-100.
57. Mwimanzi P, Markle TJ, Ogata Y, Martin E, Tokunaga M, Mahiti M, Kuang XT, Walker BD, Brockman MA, Brumme ZL, Ueno T. 2013. Dynamic range of Nef functions in chronic HIV-1 infection. Virology 439:74-80. http://dx.doi.org/10.1016/j.virol.2013.02.005.
58. Foster JL, Denial SJ, Temple BR, Garcia JV. 2011. Mechanisms of HIV-1 Nef function and intracellular signaling. J. Neuroimmune Pharmacol. 6:230-246. http://dx.doi.org/10.1007/s11481-011-9262-y.
59. Landi A, Iannucci V, Nuffel AV, Meuwissen P, Verhasselt B. 2011. One protein to rule them all: modulation of cell surface receptors and molecules by HIV Nef. Curr. HIV Res. 9:496-504. http://dx.doi.org/10.2174/157016211798842116.
60. Brumme ZL, Brumme CJ, Chui C, Mo T, Wynhoven B, Woods CK, Henrick BM, Hogg RS, Montaner JS, Harrigan PR. 2007. Effects of human leukocyte antigen class I genetic parameters on clinical outcomes and survival after initiation of highly active antiretroviral therapy. J. Infect. Dis. 195:1694-1704. http://dx.doi.org/10.1086/516789.
61. Brumme ZL, John M, Carlson JM, Brumme CJ, Chan D, Brockman MA, Swenson LC, Tao I, Szeto S, Rosato P, Sela J, Kadie CM, Frahm N, Brander C, Haas DW, Riddler SA, Haubrich R, Walker BD, Harrigan PR, Heckerman D, Mallal S. 2009. HLA-associated immune escape pathways in HIV-1 subtype B Gag, Pol and Nef proteins. PLoS One 4:e6687. http://dx.doi.org/10.1371/journal.pone.0006687.
62. Atkins KM, Thomas L, Youker RT, Harriff MJ, Pissani F, You H, Thomas G. 2008. HIV-1 Nef binds PACS-2 to assemble a multikinase cascade that triggers major histocompatibility complex class I (MHC-I) down-regulation: analysis using short interfering RNA and knock-out mice. J. Biol. Chem. 283:11772-11784. http://dx.doi.org/10.1074/jbc.M707572200.
63. Lewis MJ, Lee P, Ng HL, Yang OO. 2012. Immune selection in vitro reveals human immunodeficiency virus type 1 Nef sequence motifs important for its immune evasion function in vivo. J. Virol. 86:7126-7135. http://dx.doi.org/10.1128/JVI.00878-12.
64. Ren X, Park SY, Bonifacino JS, Hurley JH. 2014. How HIV-1 Nef hijacks the AP-2 clathrin adaptor to downregulate CD4. eLife 3:e01754. http://dx.doi.org/10.7554/eLife.01754.
65. Hoof I, Peters B, Sidney J, Pedersen LE, Sette A, Lund O, Buus S, Nielsen M. 2009. NetMHCpan, a method for MHC class I binding prediction beyond humans. Immunogenetics 61:1-13. http://dx.doi.org/10.1007/s00251-008-0341-z.
66. Nielsen M, Lundegaard C, Blicher T, Lamberth K, Harndahl M, Justesen S, Roder G, Peters B, Sette A, Lund O, Buus S. 2007. NetMHCpan, a method for quantitative predictions of peptide binding to any HLA-A and-B locus protein of known sequence. PLoS One 2:e796. http://dx.doi.org/10.1371/journal.pone.0000796.
67. Goonetilleke N, Liu MK, Salazar-Gonzalez JF, Ferrari G, Giorgi E, Ganusov VV, Keele BF, Learn GH, Turnbull EL, Salazar MG, Weinhold KJ, Moore S, CHAVI Clinical Core B, Letvin N, Haynes BF, Cohen MS, Hraber P, Bhattacharya T, Borrow P, Perelson AS, Hahn BH, Shaw GM, Korber BT, McMichael AJ. 2009. The first T cell response to transmitted/founder virus contributes to the control of acute viremia in HIV-1 infection. J. Exp. Med. 206:1253-1272. http://dx.doi.org/10.1084/jem.20090365.
68. Li F, Finnefrock AC, Dubey SA, Korber BT, Szinger J, Cole S, McElrath MJ, Shiver JW, Casimiro DR, Corey L, Self SG. 2011. Mapping HIV-1 vaccine induced T-cell responses: bias towards less-conserved regions and potential impact on vaccine efficacy in the Step study. PLoS One 6:e20479. http://dx.doi.org/10.1371/journal.pone.0020479.
69. Fischer W, Ganusov VV, Giorgi EE, Hraber PT, Keele BF, Leitner T, Han CS, Gleasner CD, Green L, Lo CC, Nag A, Wallstrom TC, Wang S, McMichael AJ, Haynes BF, Hahn BH, Perelson AS, Borrow P, Shaw GM, Bhattacharya T, Korber BT. 2010. Transmission of single HIV-1 genomes and dynamics of early immune escape revealed by ultra-deep sequencing. PLoS One 5:e12303. http://dx.doi.org/10.1371/journal.pone.0012303.
70. Henn MR, Boutwell CL, Charlebois P, Lennon NJ, Power KA, Macalalad AR, Berlin AM, Malboeuf CM, Ryan EM, Gnerre S, Zody MC, Erlich RL, Green LM, Berical A, Wang Y, Casali M, Streeck H, Bloom AK, Dudek T, Tully D, Newman R, Axten KL, Gladden AD, Battis L, Kemper M, Zeng Q, Shea TP, Gujja S, Zedlack C, Gasser O, Brander C, Hess C, Gunthard HF, Brumme ZL, Brumme CJ, Bazner S, Rychert J, Tinsley JP, Mayer KH, Rosenberg E, Pereyra F, Levin JZ, Young SK, Jessen H, Altfeld M, Birren BW, Walker BD, Allen TM. 2012. Whole genome deep sequencing of HIV-1 reveals the impact of early minor variants upon immune recognition during acute infection. PLoS Pathog. 8:e1002529. http://dx.doi.org/10.1371/journal.ppat.1002529.
71. Akari H, Arold S, Fukumori T, Okazaki T, Strebel K, Adachi A. 2000. Nef-induced major histocompatibility complex class I down-regulation is functionally dissociated from its virion incorporation, enhancement of viral infectivity, and CD4 down-regulation. J. Virol. 74:2907-2912. http://dx.doi.org/10.1128/JVI.74.6.2907-2912.2000.
72. Geyer M, Fackler OT, Peterlin BM. 2001. Structure-function relationships in HIV-1 Nef. EMBO Rep. 2:580-585. http://dx.doi.org/10.1093/embo-reports/kve141.
73. Jia X, Singh R, Homann S, Yang H, Guatelli J, Xiong Y. 2012. Structural basis of evasion of cellular adaptive immunity by HIV-1 Nef. Nat. Struct. Mol. Biol. 19:701-706. http://dx.doi.org/10.1038/nsmb.2328.
74. Kuo LS, Baugh LL, Denial SJ, Watkins RL, Liu M, Garcia JV, Foster JL. 2012. Overlapping effector interfaces define the multiple functions of the HIV-1 Nef polyproline helix. Retrovirology 9:47. http://dx.doi.org/10.1186/1742-4690-9-47.
75. Mangasarian A, Piguet V, Wang JK, Chen YL, Trono D. 1999. Nefinduced CD4 and major histocompatibility complex class I (MHC-I) down-regulation are governed by distinct determinants: N-terminal alpha helix and proline repeat of Nef selectively regulate MHC-I trafficking. J. Virol. 73:1964-1973.
76. Schaefer MR, Wonderlich ER, Roeth JF, Leonard JA, Collins KL. 2008. HIV-1 Nef targets MHC-I and CD4 for degradation via a final common beta-COP-dependent pathway in T cells. PLoS Pathog. 4:e1000131. http://dx.doi.org/10.1371/journal.ppat.1000131.
77. Yamada T, Kaji N, Odawara T, Chiba J, Iwamoto A, Kitamura Y. 2003. Proline 78 is crucial for human immunodeficiency virus type 1 Nef to down-regulate class I human leukocyte antigen. J. Virol. 77:1589-1594. http://dx.doi.org/10.1128/JVI.77.2.1589-1594.2003.
78. Chopera DR, Woodman Z, Mlisana K, Mlotshwa M, Martin DP, Seoighe C, Treurnicht F, de Rosa DA, Hide W, Karim SA, Gray CM, Williamson C, Team CS. 2008. Transmission of HIV-1 CTL escape variants provides HLA-mismatched recipients with a survival advantage. PLoS Pathog. 4:e1000033. http://dx.doi.org/10.1371/journal.ppat.1000033.
79. Goepfert PA, Lumm W, Farmer P, Matthews P, Prendergast A, Carlson JM, Derdeyn CA, Tang J, Kaslow RA, Bansal A, Yusim K, Heckerman D, Mulenga J, Allen S, Goulder PJ, Hunter E. 2008. Transmission of HIV-1 Gag immune escape mutations is associated with reduced viral load in linked recipients. J. Exp. Med. 205:1009-1017. http://dx.doi.org/10.1084/jem.20072457.
80. Fraser C, Lythgoe K, Leventhal GE, Shirreff G, Hollingsworth TD, Alizon S, Bonhoeffer S. 2014. Virulence and pathogenesis of HIV-1 infection: an evolutionary perspective. Science 343:1243727. http://dx.doi.org/10.1126/science.1243727.
81. Liu X, Schrager JA, Lange GD, Marsh JW. 2001. HIV Nef-mediated cellular phenotypes are differentially expressed as a function of intracellular Nef concentrations. J. Biol. Chem. 276:32763-32770. http://dx.doi.org/10.1074/jbc.M101025200.
82. Rajapaksa US, Li D, Peng YC, McMichael AJ, Dong T, Xu XN. 2012. HLA-B may be more protective against HIV-1 than HLA-A because it resists negative regulatory factor (Nef) mediated down-regulation. Proc. Natl. Acad. Sci. U. S. A. 109:13353-13358. http://dx.doi.org/10.1073/pnas.1204199109.