HIV fusion in dendritic cells occurs mainly at the surface and is limited by low CD4 levels

Journal of Virology

Volumn 91, Issue 21, 2017, Pages

  Chauveau, Lise ^a,b   Donahue, Daniel Aaron ^a,b   Monel, Blandine ^a,b   Porrot, Francoise ^a,b   Bruel, Timothée ^a,b   Richard, Lea ^a,b   Casartelli, Nicoletta ^a,b   Schwartz, Olivier ^a,b,c  

^a INSTITUT PASTEUR   (France)

^b Institut Pasteur   (France)

^c Vaccine Research Institute   (France)

Author keywords

Dendritic cells; Human immunodeficiency virus; Virus entry

Indexed keywords

CHEMOKINE RECEPTOR CXCR4; LYSOSOME ASSOCIATED MEMBRANE PROTEIN 1; TOLL LIKE RECEPTOR 7; CD4 ANTIGEN; VIRUS RECEPTOR;

ADAPTIVE IMMUNITY; ANTIGEN PRESENTING CELL; ARTICLE; BONE MARROW CELL; CELL FUSION; CELL INTERACTION; CELL MEMBRANE PERMEABILITY; CELLULAR DISTRIBUTION; CONTROLLED STUDY; DENDRITIC CELL; HUMAN IMMUNODEFICIENCY VIRUS 1; INTERNALIZATION; MEMBRANE PERMEABILITY; NONHUMAN; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN LOCALIZATION; SIGNAL TRANSDUCTION; VIRUS ENTRY; VIRUS PARTICLE; VIRUS STRAIN; CELL CULTURE; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; METABOLISM; PHYSIOLOGY; VIROLOGY; VIRUS REPLICATION;

CD4 ANTIGENS; CELL FUSION; CELLS, CULTURED; DENDRITIC CELLS; HIV INFECTIONS; HIV-1; HUMANS; RECEPTORS, HIV; TOLL-LIKE RECEPTOR 7; VIRUS REPLICATION;

EID: 85031117064     PISSN: 0022538X     EISSN: 10985514     Source Type: Journal    
DOI: 10.1128/JVI.01248-17     Document Type: Article

References (72)

1. Buseyne F, Le Gall S, Boccaccio C, Abastado JP, Lifson JD, Arthur LO, Rivière Y, Heard JM, Schwartz O. 2001. MHC-I-restricted presentation of HIV-1 virion antigens without viral replication. Nat Med 7:344-349. https://doi.org/10.1038/85493
2. Alloatti A, Kotsias F, Magalhaes JG, Amigorena S. 2016. Dendritic cell maturation and cross-presentation: timing matters! Immunol Rev 272: 97-108. https://doi.org/10.1111/imr.12432
3. Guilliams M, Ginhoux F, Jakubzick C, Naik SH, Onai N, Schraml BU, Segura E, Tussiwand R, Yona S. 2014. Dendritic cells, monocytes and macrophages: a unified nomenclature based on ontogeny. Nat Rev Immunol 14:571-578. https://doi.org/10.1038/nri3712
4. Segura E, Amigorena S. 2015. Cross-presentation in mouse and human dendritic cells. Adv Immunol 127:1-31. https://doi.org/10.1016/bs.ai .2015.03.002
5. Villani A-CC, Satija R, Reynolds G, Sarkizova S, Shekhar K, Fletcher J, Griesbeck M, Butler A, Zheng S, Lazo S, Jardine L, Dixon D, Stephenson E, Nilsson E, Grundberg I, McDonald D, Filby A, Li W, De Jager PL, Rozenblatt-Rosen O, Lane AA, Haniffa M, Regev A, Hacohen N. 2017. Single-cell RNA-seq reveals new types of human blood dendritic cells, monocytes, and progenitors. Science 356:eaah4573. https://doi.org/10 .1126/science.aah4573
6. See P, Dutertre C-AA, Chen J, Günther P, McGovern N, Irac SE, Gunawan M, Beyer M, Händler K, Duan K, Sumatoh HRB, Ruffin N, Jouve M, Gea-Mallorquí E, Hennekam RCM, Lim T, Yip CC, Wen M, Malleret B, Low I, Shadan NB, Fen CFS, Tay A, Lum J, Zolezzi F, Larbi A, Poidinger M, Chan JKY, Chen Q, Rénia L, Haniffa M, Benaroch P, Schlitzer A, Schultze JL, Newell EW, Ginhoux F. 2017. Mapping the human DC lineage through the integration of high-dimensional techniques. Science 356:eaag3009. https://doi.org/10.1126/science.aag3009
7. Ahmed Z, Kawamura T, Shimada S, Piguet V. 2015. The role of human dendritic cells in HIV-1 infection. J Investig Dermatol 135:1225-1233. https://doi.org/10.1038/jid.2014.490
8. Piguet V, Steinman RM. 2007. The interaction of HIV with dendritic cells: outcomes and pathways. Trends Immunol 28:503-510. https://doi.org/10.1016/j.it.2007.07.010
9. Wu L, KewalRamani VN. 2006. Dendritic-cell interactions with HIV: infection and viral dissemination. Nat Rev Immunol 6:859-868. https://doi .org/10.1038/nri1960
10. Izquierdo-Useros N, Lorizate M, McLaren PJ, Telenti A, Krausslich HG, Martinez-Picado J. 2014. HIV-1 capture and transmission by dendritic cells: the role of viral glycolipids and the cellular receptor Siglec-1. PLoS Pathog 10:e1004146. https://doi.org/10.1371/journal.ppat.1004146
11. Puryear WB, Akiyama H, Geer SD, Ramirez NP, Yu X, Reinhard BMM, Gummuluru S. 2013. Interferon-inducible mechanism of dendritic cellmediated HIV-1 dissemination is dependent on Siglec-1/CD169. PLoS Pathog 9:e1003291. https://doi.org/10.1371/journal.ppat.1003291
12. Lahouassa H, Daddacha W, Hofmann H, Ayinde D, Logue EC, Dragin L, Bloch N, Maudet C, Bertrand M, Gramberg T, Pancino G, Priet S, Canard B, Laguette N, Benkirane M, Transy C, Landau NR, Kim B, Margottin-Goguet F. 2012. SAMHD1 restricts the replication of human immunodeficiency virus type 1 by depleting the intracellular pool of deoxynucleoside triphosphates. Nat Immunol 13:223-228. https://doi.org/10.1038/ni .2236
13. Goujon C, Jarrosson-Wuilleme L, Bernaud J, Rigal D, Darlix JL, Cimarelli A. 2006. With a little help from a friend: increasing HIV transduction of monocyte-derived dendritic cells with virion-like particles of SIV(MAC). Gene Ther 13:991-994. https://doi.org/10.1038/sj.gt.3302753
14. Laguette N, Sobhian B, Casartelli N, Ringeard M, Chable-Bessia C, Segeral E, Yatim A, Emiliani S, Schwartz O, Benkirane M. 2011. SAMHD1 is the dendritic-and myeloid-cell-specific HIV-1 restriction factor counteracted by Vpx. Nature 474:654-657. https://doi.org/10.1038/nature10117
15. Hrecka K, Hao C, Gierszewska M, Swanson SK, Kesik-Brodacka M, Srivastava S, Florens L, Washburn MP, Skowronski J. 2011. Vpx relieves inhibition of HIV-1 infection of macrophages mediated by the SAMHD1 protein. Nature 474:658-661. https://doi.org/10.1038/nature10195
16. McIlroy D, Autran B, Cheynier R, Wain-Hobson S, Clauvel JP, Oksenhendler E, Debré P, Hosmalin A. 1995. Infection frequency of dendritic cells and CD4+ T lymphocytes in spleens of human immunodeficiency viruspositive patients. J Virol 69:4737-4745
17. Donaghy H, Gazzard B, Gotch F, Patterson S. 2003. Dysfunction and infection of freshly isolated blood myeloid and plasmacytoid dendritic cells in patients infected with HIV-1. Blood 101:4505-4511. https://doi .org/10.1182/blood-2002-10-3189
18. Calantone N, Wu F, Klase Z, Deleage C, Perkins M, Matsuda K, Thompson EA, Ortiz AM, Vinton CL, Ourmanov I, Lore K, Douek DC, Estes JD, Hirsch VM, Brenchley JM. 2014. Tissue myeloid cells in SIV-infected primates acquire viral DNA through phagocytosis of infected T cells. Immunity 41:493-502. https://doi.org/10.1016/j.immuni.2014.08.014
19. Shingai M, Welbourn S, Brenchley JM, Acharya P, Miyagi E, Plishka RJ, Buckler-White A, Kwong PD, Nishimura Y, Strebel K, Martin MA. 2015. The expression of functional Vpx during pathogenic SIVmac infections of rhesus macaques suppresses SAMHD1 in CD4+ memory T cells. PLoS Pathog 11:e1004928. https://doi.org/10.1371/journal.ppat.1004928
20. Chauveau L, Puigdomenech I, Ayinde D, Roesch F, Porrot F, Bruni D, Visseaux B, Descamps D, Schwartz O. 2015. HIV-2 infects resting CD4+ T cells but not monocyte-derived dendritic cells. Retrovirology 12:2. https://doi.org/10.1186/s12977-014-0131-7
21. Smed-Sorensen A, Lore K, Vasudevan J, Louder MK, Andersson J, Mascola JR, Spetz AL, Koup RA. 2005. Differential susceptibility to human immunodeficiency virus type 1 infection of myeloid and plasmacytoid dendritic cells. J Virol 79:8861-8869. https://doi.org/10.1128/JVI.79.14 .8861-8869.2005
22. Granelli-Piperno A, Shimeliovich I, Pack M, Trumpfheller C, Steinman RM. 2006. HIV-1 selectively infects a subset of nonmaturing BDCA1-positive dendritic cells in human blood. J Immunol 176:991-998. https://doi.org/10.4049/jimmunol.176.2.991
23. Duvall MG, Lore K, Blaak H, Ambrozak DA, Adams WC, Santos K, Geldmacher C, Mascola JR, McMichael AJ, Jaye A, Whittle HC, Rowland-Jones SL, Koup RA. 2007. Dendritic cells are less susceptible to human immunodeficiency virus type 2 (HIV-2) infection than to HIV-1 infection. J Virol 81:13486-13498. https://doi.org/10.1128/JVI.00976-07
24. Lahaye X, Satoh T, Gentili M, Cerboni S, Conrad C, Hurbain I, El Marjou A, Lacabaratz C, Lelievre JD, Manel N. 2013. The capsids of HIV-1 and HIV-2 determine immune detection of the viral cDNA by the innate sensor cGAS in dendritic cells. Immunity 39:1132-1142. https://doi.org/10.1016/j.immuni.2013.11.002
25. Manel N, Hogstad B, Wang Y, Levy DE, Unutmaz D, Littman DR. 2010. A cryptic sensor for HIV-1 activates antiviral innate immunity in dendritic cells. Nature 467:214-217. https://doi.org/10.1038/nature09337
26. Silvin A, Yu CI, Lahaye X, Imperatore F, Brault J-B, Cardinaud S, Becker C, Kwan W-H, Conrad C, Maurin M, Goudot C, Marques-Ladeira S, Wang Y, Pascual V, Anguiano E, Albrecht RA, Iannacone M, García-Sastre A, Goud B, Dalod M, Moris A, Merad M, Palucka AK, Manel N. 2017. Constitutive resistance to viral infection in human CD141+ dendritic cells. Sci Immunol 2:eaai8071
27. Herold N, Anders-Osswein M, Glass B, Eckhardt M, Muller B, Krausslich HG. 2014. HIV-1 entry in SupT1-R5, CEM-ss, and primary CD4+ T cells occurs at the plasma membrane and does not require endocytosis. J Virol 88:13956-13970. https://doi.org/10.1128/JVI.01543-14
28. Marin M, Melikyan GB. 2015. Can HIV-1 entry sites be deduced by comparing bulk endocytosis to functional readouts for viral fusion? J Virol 89:2985. https://doi.org/10.1128/JVI.03352-14
29. Sattentau QJ. 2010. Cell-to-cell spread of retroviruses. Viruses 2:1306-1321. https://doi.org/10.3390/v2061306
30. Miyauchi K, Kim Y, Latinovic O, Morozov V, Melikyan GB. 2009. HIV enters cells via endocytosis and dynamin-dependent fusion with endosomes. Cell 137:433-444. https://doi.org/10.1016/j.cell.2009.02.046
31. de la Vega M, Marin M, Kondo N, Miyauchi K, Kim Y, Epand RF, Epand RM, Melikyan GB. 2011. Inhibition of HIV-1 endocytosis allows lipid mixing at the plasma membrane, but not complete fusion. Retrovirology 8:99. https://doi.org/10.1186/1742-4690-8-99
32. Lee B, Sharron M, Montaner LJ, Weissman D, Doms RW. 1999. Quantification of CD4, CCR5, and CXCR4 levels on lymphocyte subsets, dendritic cells, and differentially conditioned monocyte-derived macrophages. Proc Natl Acad Sci U S A 96:5215-5220. https://doi.org/10.1073/pnas.96 .9.5215
33. Patterson S, Gross J, English N, Stackpoole A, Bedford P, Knight SC. 1995. CD4 expression on dendritic cells and their infection by human immunodeficiency virus. J Gen Virol 76:1155-1163. https://doi.org/10.1099/0022-1317-76-5-1155
34. Janas AM, Dong C, Wang J-HH, Wu L. 2008. Productive infection of human immunodeficiency virus type 1 in dendritic cells requires fusionmediated viral entry. Virology 375:442-451. https://doi.org/10.1016/j .virol.2008.01.044
35. Melikyan GB, Markosyan RM, Hemmati H, Delmedico MK, Lambert DM, Cohen FS. 2000. Evidence that the transition of HIV-1 gp41 into a six-helix bundle, not the bundle configuration, induces membrane fusion. J Cell Biol 151:413-423. https://doi.org/10.1083/jcb.151.2.413
36. Wang J-HH, Wells C, Wu L. 2008. Macropinocytosis and cytoskeleton contribute to dendritic cell-mediated HIV-1 transmission to CD4+ T cells. Virology 381:143-154. https://doi.org/10.1016/j.virol.2008.08.028
37. Ménager MMM, Littman DR. 2016. Actin dynamics regulates dendritic cell-mediated transfer of HIV-1 to T cells. Cell 164:695-709. https://doi .org/10.1016/j.cell.2015.12.036
38. Moris A, Nobile C, Buseyne F, Porrot F, Abastado JP, Schwartz O. 2004. DC-SIGN promotes exogenous MHC-I-restricted HIV-1 antigen presentation. Blood 103:2648-2654. https://doi.org/10.1182/blood-2003-07-2532
39. Luban J. 2012. Innate immune sensing of HIV-1 by dendritic cells. Cell Host Microbe 12:408-418. https://doi.org/10.1016/j.chom.2012.10.002
40. Veiga S, Henriques S, Santos NC, Castanho M. 2004. Putative role of membranes in the HIV fusion inhibitor enfuvirtide mode of action at the molecular level. Biochem J 377:107-110. https://doi.org/10.1042/bj20031350
41. Lazzarin A. 2005. Enfuvirtide: the first HIV fusion inhibitor. Expert Opin Pharmacother 6:453-464. https://doi.org/10.1517/14656566.6.3.453
42. Cavrois M, De Noronha C, Greene WC. 2002. A sensitive and specific enzyme-based assay detecting HIV-1 virion fusion in primary T lymphocytes. Nat Biotechnol 20:1151-1154. https://doi.org/10.1038/nbt745
43. Passaes CP, Bruel T, Decalf J, David A, Angin M, Monceaux V, Muller-Trutwin M, Noel N, Bourdic K, Lambotte O, Albert ML, Duffy D, Schwartz O, Saez-Cirion A, ANRS RHIVIERA Consortium. 2017. Ultrasensitive HIV-1 p24 assay detects single infected cells and differences in reservoir induction by latency reversal agents. J Virol 91:e02296-16. https://doi .org/10.1128/JVI.02296-16
44. Aggarwal A, Hitchen TL, Ootes L, McAllery S, Wong A, Nguyen K, McCluskey A, Robinson PJ, Turville SG. 2017. HIV infection is influenced by dynamin at 3 independent points in the viral life cycle. Traffic 18:392-410. https://doi.org/10.1111/tra.12481
45. Pion M, Arrighi JF, Jiang J, Lundquist CA, Hartley O, Aiken C, Piguet V. 2007. Analysis of HIV-1-X4 fusion with immature dendritic cells identifies a specific restriction that is independent of CXCR4 levels. J Investig Dermatol 127:319-323. https://doi.org/10.1038/sj.jid.5700518
46. Dong C, Janas AM, Wang JH, Olson WJ, Wu L. 2007. Characterization of human immunodeficiency virus type 1 replication in immature and mature dendritic cells reveals dissociable cis-and trans-infection. J Virol 81:11352-11362. https://doi.org/10.1128/JVI.01081-07
47. Joseph SB, Arrildt KT, Swanstrom AE, Schnell G, Lee B, Hoxie JA, Swanstrom R. 2014. Quantification of entry phenotypes of macrophage-tropic HIV-1 across a wide range of CD4 densities. J Virol 88:1858-1869. https://doi.org/10.1128/JVI.02477-13
48. Rowell JF, Ruff AL, Guarnieri FG, Staveley-O'Carroll K, Lin X, Tang J, August JT, Siliciano RF. 1995. Lysosome-associated membrane protein-1-mediated targeting of the HIV-1 envelope protein to an endosomal/lysosomal compartment enhances its presentation to MHC class IIrestricted T cells. J Immunol 155:1818-1828
49. O'Brien M, Manches O, Wilen C, Gopal R, Huq R, Wu V, Sunseri N, Bhardwaj N. 2016. CD4 receptor is a key determinant of divergent HIV-1 sensing by plasmacytoid dendritic cells. PLoS Pathog 12:e1005553. https://doi.org/10 .1371/journal.ppat.1005553
50. Eskelinen E-LL. 2006. Roles of LAMP-1 and LAMP-2 in lysosome biogenesis and autophagy. Mol Aspects Med 27:495-502. https://doi.org/10 .1016/j.mam.2006.08.005
51. Ewald SE, Barton GM. 2011. Nucleic acid sensing Toll-like receptors in autoimmunity. Curr Opin Immunol 23:3-9. https://doi.org/10.1016/j.coi .2010.11.006
52. Gay NJ, Symmons MF, Gangloff M, Bryant CE. 2014. Assembly and localization of Toll-like receptor signalling complexes. Nat Rev Immunol 14:546-558. https://doi.org/10.1038/nri3713
53. Gleeson PA. 2014. The role of endosomes in innate and adaptive immunity. Semin Cell Dev Biol 31:64-72. https://doi.org/10.1016/j.semcdb .2014.03.002
54. Donahue DA, Amraoui S, di Nunzio F, Kieffer C, Porrot F, Opp S, Diaz-Griffero F, Casartelli N, Schwartz O. 2016. SUN2 overexpression deforms nuclear shape and inhibits HIV. J Virol 90:4199-4214. https://doi.org/10 .1128/JVI.03202-15
55. Maréchal V, Clavel F, Heard JM, Schwartz O. 1998. Cytosolic Gag p24 as an index of productive entry of human immunodeficiency virus type 1. J Virol 72:2208-2212
56. Cavrois M, Neidleman J, Kreisberg JF, Fenard D, Callebaut C, Greene WC. 2006. Human immunodeficiency virus fusion to dendritic cells declines as cells mature. J Virol 80:1992-1999. https://doi.org/10.1128/JVI.80.4 .1992-1999.2006
57. Yu HJ, Reuter MA, McDonald D. 2008. HIV traffics through a specialized, surface-accessible intracellular compartment during trans-infection of T cells by mature dendritic cells. PLoS Pathog 4:e1000134. https://doi.org/10.1371/journal.ppat.1000134
58. Garcia E, Pion M, Pelchen-Matthews A, Collinson L, Arrighi J-FF, Blot G, Leuba F, Escola J-MM, Demaurex N, Marsh M, Piguet V. 2005. HIV-1 trafficking to the dendritic cell-T-cell infectious synapse uses a pathway of tetraspanin sorting to the immunological synapse. Traffic 6:488-501. https://doi.org/10.1111/j.1600-0854.2005.00293.x
59. Izquierdo-Useros N, Naranjo-Gomez M, Archer J, Hatch SC, Erkizia I, Blanco J, Borras FE, Puertas MC, Connor JH, Fernandez-Figueras MT, Moore L, Clotet B, Gummuluru S, Martinez-Picado J. 2009. Capture and transfer of HIV-1 particles by mature dendritic cells converges with the exosome-dissemination pathway. Blood 113:2732-2741. https://doi.org/10.1182/blood-2008-05-158642
60. Gummuluru S, Ramirez GN, Akiyama H. 2014. CD169-dependent cellassociated HIV-1 transmission: a driver of virus dissemination. J Infect Dis 210(Suppl 3):S641-S647. https://doi.org/10.1093/infdis/jiu442
61. Nobile C, Moris A, Porrot F, Sol-Foulon N, Schwartz O. 2003. Inhibition of human immunodeficiency virus type 1 Env-mediated fusion by DC-SIGN. J Virol 77:5313-5323. https://doi.org/10.1128/JVI.77.9.5313-5323.2003
62. Granelli-Piperno A, Moser B, Pope M, Chen D, Wei Y, Isdell F, O'Doherty U, Paxton W, Koup R, Mojsov S, Bhardwaj N, Clark-Lewis I, Baggiolini M, Steinman RM. 1996. Efficient interaction of HIV-1 with purified dendritic cells via multiple chemokine coreceptors. J Exp Med 184:2433-2438. https://doi.org/10.1084/jem.184.6.2433
63. Rubbert A, Combadiere C, Ostrowski M, Arthos J, Dybul M, Machado E, Cohn MA, Hoxie JA, Murphy PM, Fauci AS, Weissman D. 1998. Dendritic cells express multiple chemokine receptors used as coreceptors for HIV entry. J Immunol 160:3933-3941
64. Nobile C, Petit C, Moris A, Skrabal K, Abastado JP, Mammano F, Schwartz O. 2005. Covert human immunodeficiency virus replication in dendritic cells and in DC-SIGN-expressing cells promotes long-term transmission to lymphocytes. J Virol 79:5386-5399. https://doi.org/10.1128/JVI.79.9 .5386-5399.2005
65. Turville SG, Santos JJ, Frank I, Cameron PU, Wilkinson J, Miranda-Saksena M, Dable J, Stossel H, Romani N, Piatak M, Jr, Lifson JD, Pope M, Cunningham AL. 2004. Immunodeficiency virus uptake, turnover, and 2-phase transfer in human dendritic cells. Blood 103:2170-2179. https://doi.org/10.1182/blood-2003-09-3129
66. Moris A, Pajot A, Blanchet F, Guivel-Benhassine F, Salcedo M, Schwartz O. 2006. Dendritic cells and HIV-specific CD4+ T cells: HIV antigen presentation, T cell activation, viral transfer. Blood 108:1643-1651. https://doi .org/10.1182/blood-2006-02-006361
67. Iwasaki A. 2012. Innate immune recognition of HIV-1. Immunity 37: 389-398. https://doi.org/10.1016/j.immuni.2012.08.011
68. Bruni D, Chazal M, Sinigaglia L, Chauveau L, Schwartz O, Despres P, Jouvenet N. 2015. Viral entry route determines how human plasmacytoid dendritic cells produce type I interferons. Sci Signal 8:ra25. https://doi.org/10.1126/scisignal.aaa1552
69. Beauparlant D, Rusert P, Magnus C, Kadelka C, Weber J, Uhr T, Zagordi O, Oberle C, Duenas-Decamp MJ, Clapham PR, Metzner KJ, Günthard HF, Trkola A. 2017. Delineating CD4 dependency of HIV-1: adaptation to infect low level CD4 expressing target cells widens cellular tropism but severely impacts on envelope functionality. PLoS Pathog 13:e1006255. https://doi.org/10.1371/journal.ppat.1006255
70. Massanella M, Puigdomènech I, Cabrera C, Fernandez-Figueras MT, Aucher A, Gaibelet G, Hudrisier D, García E, Bofill M, Clotet B, Blanco J. 2009. Antigp41 antibodies fail to block early events of virological synapses but inhibit HIV spread between T cells. AIDS 23:183-188. https://doi.org/10.1097/QAD.0b013e32831ef1a3
71. Reuter S, Kaumanns P, Buschhorn SB, Dittmar MT. 2005. Role of HIV-2 envelope in Lv2-mediated restriction. Virology 332:347-358. https://doi .org/10.1016/j.virol.2004.11.025
72. Sol-Foulon N, Esnault C, Percherancier Y, Porrot F, Metais-Cunha P, Bachelerie F, Schwartz O. 2004. The effects of HIV-1 Nef on CD4 surface expression and viral infectivity in lymphoid cells are independent of rafts. J Biol Chem 279:31398-31408. https://doi.org/10.1074/jbc .M401621200