The cholesterol-binding motif of the HIV-1 glycoprotein gp41 regulates lateral sorting and oligomerization

Cellular Microbiology

Volumn 16, Issue 10, 2014, Pages 1565-1581

  Schwarzer, Roland ^a   Levental, Ilya ^b   Gramatica, Andrea ^a   Scolari, Silvia ^a   Buschmann, Volker ^c   Veit, Michael ^d   Herrmann, Andreas ^a  

^a HUMBOLDT UNIVERSITY   (Germany)

^b UNIVERSITY OF TEXAS MEDICAL SCHOOL   (United States)

^c PICOQUANT GMBH   (Germany)

^d FREIE UNIVERSITÄT BERLIN   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

GLYCOPROTEIN GP 41; GLYCOSYLPHOSPHATIDYLINOSITOL; PROTEIN VARIANT; CHOLESTEROL; GP41 PROTEIN, HUMAN IMMUNODEFICIENCY VIRUS 1;

ANIMAL CELL; ANISOTROPY; ARTICLE; CELL HETEROGENEITY; CELL MEMBRANE; CELLULAR DISTRIBUTION; CHO CELL LINE; CHOLESTEROL RECOGNITION AMINO ACID CONSENSUS; CONSENSUS SEQUENCE; CONTROLLED STUDY; FLUORESCENCE LIFETIME IMAGING MICROSCOPY; FLUORESCENCE MICROSCOPY; FLUORESCENCE POLARIZATION MICROSCOPY; FLUORESCENCE RESONANCE ENERGY TRANSFER; GOLGI COMPLEX; HUMAN IMMUNODEFICIENCY VIRUS 1; LIPID RAFT; NONHUMAN; OLIGOMERIZATION; PROTEIN FUNCTION; PROTEIN MOTIF; REGULATORY MECHANISM; VIRUS ASSEMBLY; ANIMAL; CELL LINE; CRICETULUS; HAMSTER; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; METABOLISM; PATHOGENICITY; PROTEIN TERTIARY STRUCTURE; TRANSMISSION; VIROLOGY; VIRUS ATTACHMENT;

ANIMALS; CELL LINE; CELL MEMBRANE; CHO CELLS; CHOLESTEROL; CRICETINAE; CRICETULUS; FLUORESCENCE RESONANCE ENERGY TRANSFER; HIV ENVELOPE PROTEIN GP41; HIV INFECTIONS; HIV-1; MEMBRANE MICRODOMAINS; MICROSCOPY, FLUORESCENCE; PROTEIN STRUCTURE, TERTIARY; VIRUS ATTACHMENT;

EID: 84908079451     PISSN: 14625814     EISSN: 14625822     Source Type: Journal    
DOI: 10.1111/cmi.12314     Document Type: Article

References (93)

1. Abad, C., Martínez-Gil, L., Tamborero, S., and Mingarro, I. (2009) Membrane topology of gp41 and amyloid precursor protein: interfering transmembrane interactions as potential targets for HIV and Alzheimer treatment. Biochim Biophys Acta 1788: 2132-2141.
2. Aloia, R.C., Tian, H., and Jensen, F.C. (1993) Lipid composition and fluidity of the human immunodeficiency virus envelope and host cell plasma membranes. Proc Natl Acad Sci USA 90: 5181-5185.
3. Berlioz-Torrent, C., Shacklett, B.L., Erdtmann, L., Delamarre, L., Bouchaert, I., Sonigo, P., et al. (1999) Interactions of the cytoplasmic domains of human and simian retroviral transmembrane proteins with components of the clathrin adaptor complexes modulate intracellular and cell surface expression of envelope glycoproteins. J Virol 73: 1350- 1361.
4. Bernstein, H.B., Tucker, S.P., Kar, S.R., McPherson, S.A., McPherson, D.T., Dubay, J.W., et al. (1995) Oligomerization of the hydrophobic heptad repeat of gp41. J Virol 69: 2745-2750.
5. Bhattacharya, J., Peters, P., and Clapham, P. (2004) immunodeficiency virus type 1 envelope glycoproteins that lack cytoplasmic domain cysteines: impact on association with membrane lipid rafts and incorporation onto. J Virol 78: 5500-5506.
6. Bhattacharya, J., Repik, A., and Clapham, P.R. (2006) Gag regulates association of human immunodeficiency virus type 1 envelope with detergent-resistant membranes. J Virol 80: 5292-5300.
7. Borst, J.W., Willemse, M., Slijkhuis, R., Krogt, G., van der Laptenok, S.P., Jalink, K., et al. (2010) ATP changes the fluorescence lifetime of cyan fluorescent protein via an interaction with His148. PLoS ONE 5: e13862.
8. Brügger, B., Glass, B., Haberkant, P., Leibrecht, I., Wieland, F.T., and Kräusslich, H.-G. (2006) The HIV lipidome: a raft with an unusual composition. Proc Natl Acad Sci USA 103: 2641-2646.
9. Buschmann, V., Bleckmann, A., Bülter, A., Krämer, B., Nikolaus, J., Roland, S., et al. (n.d.) Polarization Extension Unit for LSM Upgrade Kits. Available from URL: http:// www.picoquant.com/images/uploads/page/files/7257/ technote_polarization_extension_lsm.pdf.
10. Byland, R., Vance, P.J., Hoxie, J.A., and Marsh, M. (2007) A conserved dileucine motif mediates clathrin and AP-2- dependent endocytosis of the HIV-1 envelope protein. Mol Biol Cell 18: 414-425.
11. Campbell, S., Oshima, M., Mirro, J., Nagashima, K., and Rein, A. (2002) Reversal by dithiothreitol treatment of the block in murine leukemia virus maturation induced by disulfide cross-linking. J Virol 76: 10050-10055.
12. Campbell, S., Gaus, K., Bittman, R., Jessup, W., Crowe, S., and Mak, J. (2004) The raft-promoting property of virionassociated cholesterol, but not the presence of virionassociated Brij 98 rafts, is a determinant of human immunodeficiency virus type 1 infectivity. J Virol 78: 10556-10565.
13. Campbell, S.M., Crowe, S.M., and Mak, J. (2002) Virionassociated cholesterol is critical for the maintenance of HIV-1 structure and infectivity. AIDS 16: 2253-2261.
14. Center, R.J., Kemp, B.E., and Poumbourios, P. (1997) Human immunodeficiency virus type 1 and 2 envelope glycoproteins oligomerize through conserved sequences. J Virol 71: 5706-5711.
15. Chan, W., Lin, H., and Chen, S. (2005) Wild-type-like viral replication potential of human immunodeficiency virus type 1 envelope mutants lacking palmitoylation signals. J Virol 79: 8374-8387.
16. Checkley, M.A., Luttge, B.G., and Freed, E.O. (2011) HIV-1 envelope glycoprotein biosynthesis, trafficking, and incorporation. J Mol Biol 410: 582-608.
17. Chen, S.S., Lee, S.F., and Wang, C.T. (2001) Cellular membrane-binding ability of the C-terminal cytoplasmic domain of human immunodeficiency virus type 1 envelope transmembrane protein gp41. J Virol 75: 9925-9938.
18. Chen, S.S.-L., Yang, P., Ke, P.-Y., Li, H.-F., Chan, W.-E., Chang, D.-K., et al. (2009) Identification of the LWYIK motif located in the human immunodeficiency virus type 1 transmembrane gp41 protein as a distinct determinant for viral infection. J Virol 83: 870-883.
19. Day, J.R., Van Damme, N., and Guatelli, J.C. (2006) The effect of the membrane-proximal tyrosine-based sorting signal of HIV-1 gp41 on viral infectivity depends on sequences within gp120. Virology 354: 316-327.
20. Dubay, J.W., Roberts, S.J., Hahn, B.H., and Hunter, E. (1992) Truncation of the human immunodeficiency virus type 1 transmembrane glycoprotein cytoplasmic domain blocks virus infectivity. J Virol 66: 6616-6625.
21. Earl, P.L., Doms, R.W., and Moss, B. (1990) Oligomeric structure of the human immunodeficiency virus type 1 envelope glycoprotein. Proc Natl Acad Sci USA 87: 648- 652.
22. Earl, P.L., Koenig, S., and Moss, B. (1991) Biological and immunological properties of human immunodeficiency virus type 1 envelope glycoprotein: analysis of proteins with truncations and deletions expressed by recombinant vaccinia viruses. J Virol 65: 31-41.
23. Engel, S., Scolari, S., Thaa, B., Krebs, N., Korte, T., Herrmann, A., and Veit, M. (2010) FLIM-FRET and FRAP reveal association of influenza virus haemagglutinin with membrane rafts. Biochem J 425: 567-573.
24. Epand, R., and Thomas, A. (2006) Juxtamembrane protein segments that contribute to recruitment of cholesterol into domains. Biochemistry 45: 6105-6114.
25. Epand, R.M. (2008) Proteins and cholesterol-rich domains. Biochim Biophys Acta 1778: 1576-1582.
26. Gao, F., Morrison, S.G., Robertson, D.L., Thornton, C.L., Craig, S., Karlsson, G., et al. (1996) Molecular cloning and analysis of functional envelope genes from human immunodeficiency virus type 1 sequence subtypes A through G. The WHO and NIAID Networks for HIV Isolation and Characterization. J Virol 70: 1651-1667.
27. Graham, D.R.M., Chertova, E., Hilburn, J.M., Arthur, L.O., and Hildreth, J.E.K. (2003) Cholesterol depletion of human immunodeficiency virus type 1 and simian immunodeficiency virus with-cyclodextrin inactivates and permeabilizes the virions: evidence for virion-associated lipid rafts. J Virol 77: 8237-8248.
28. Guyader, M., Kiyokawa, E., Abrami, L., Turelli, P., and Trono, D. (2002) Role for human immunodeficiency virus type 1 membrane cholesterol in viral internalization. J Virol 76: 10356-10364.
29. Hyun Bae, J., Rubini, M., Jung, G., Wiegand, G., Seifert, M.H.J., Azim, M.K., et al. (2003) Expansion of the genetic code enables design of a novel 'gold' class of green fluorescent proteins. J Mol Biol 328: 1071-1081.
30. Keller, P., Toomre, D., Díaz, E., White, J., and Simons, K. (2001) Multicolour imaging of post-Golgi sorting and trafficking in live cells. Nat Cell Biol 3: 140-149.
31. Kellner, R.R., Baier, C.J., Willig, K.I., Hell, S.W., and Barrantes, F.J. (2007) Nanoscale organization of nicotinic acetylcholine receptors revealed by stimulated emission depletion microscopy. Neuroscience 144: 135-143.
32. Kim, J.H., Hartley, T.L., Curran, A.R., and Engelman, D.M. (2009) Molecular dynamics studies of the transmembrane domain of gp41 from HIV-1. Biochim Biophys Acta 1788: 1804-1812.
33. Koga, Y., Sasaki, M., Yoshida, H., Oh-Tsu, M., Kimura, G., and Nomoto, K. (1991) Disturbance of nuclear transport of proteins in CD4+ cells expressing gp160 of human immunodeficiency virus. J Virol 65: 5609-5612.
34. Lenz, O., Dittmar, M.T., Wagner, A., Ferko, B., Vorauer-Uhl, K., Stiegler, G., and Weissenhorn, W. (2005) Trimeric membrane-anchored gp41 inhibits HIV membrane fusion. J Biol Chem 280: 4095-4101.
35. Levental, I., Grzybek, M., and Simons, K. (2010a) Greasing their way: lipid modifications determine protein association with membrane rafts. Biochemistry 49: 6305-6316.
36. Levental, I., Lingwood, D., Grzybek, M., Coskun, U., and Simons, K. (2010b) Palmitoylation regulates raft affinity for the majority of integral raft proteins. Proc Natl Acad Sci USA 107: 22050-22054.
37. Liao, Z., Graham, D.R., and Hildreth, J.E.K. (2003) Lipid rafts and HIV pathogenesis: virion-associated cholesterol is required for fusion and infection of susceptible cells. AIDS Res Hum Retroviruses 19: 675-687.
38. Lichtenberg, D., Goñi, F.M., and Heerklotz, H. (2005) Detergent-resistant membranes should not be identified with membrane rafts. Trends Biochem Sci 30: 430-436.
39. Lifson, J.D., Reyes, G.R., McGrath, M.S., Stein, B.S., and Engleman, E.G. (1986) AIDS retrovirus induced cytopathology: giant cell formation and involvement of CD4 antigen. Science 232: 1123-1127.
40. Linstedt, A.D., Foguet, M., Renz, M., Seelig, H.P., Glick, B.S., and Hauri, H.P. (1995) A C-terminally-anchored Golgi protein is inserted into the endoplasmic reticulum and then transported to the Golgi apparatus. Proc Natl Acad Sci USA 92: 5102-5105.
41. Liu, J., and Lu, M. (2010) Structure of the HIV-1 gp41 membrane-proximal ectodomain region in a putative prefusion conformation. Structure 48: 2915-2923.
42. Liu, J., Deng, Y., Li, Q., Dey, A.K., Moore, J.P., and Lu, M. (2010) Role of a putative gp41 dimerization domain in human immunodeficiency virus type 1 membrane fusion. J Virol 84: 201-209.
43. Lopez-Vergès, S., Camus, G., Blot, G., Beauvoir, R., Benarous, R., and Berlioz-Torrent, C. (2006) Tailinteracting protein TIP47 is a connector between Gag and Env and is required for Env incorporation into HIV-1 virions. Proc Natl Acad Sci USA 103: 14947-14952.
44. McInerney, T.L., El Ahmar, W., Kemp, B.E., and Poumbourios, P. (1998) Mutation-directed chemical crosslinking of human immunodeficiency virus type 1 gp41 oligomers. J Virol 72: 1523-1533.
45. Mañes, S., del Real, G., Lacalle, R.A., Lucas, P., Gómez-Moutón, C., Sánchez-Palomino, S., et al. (2000) Membrane raft microdomains mediate lateral assemblies required for HIV-1 infection. EMBO Rep 1: 190-196.
46. Mukherjee, S., Zha, X., Tabas, I., and Maxfield, F.R. (1998) Cholesterol distribution in living cells: fluorescence imaging using dehydroergosterol as a fluorescent cholesterol analog. Biophys J 75: 1915-1925.
47. Muranyi, W., Malkusch, S., Müller, B., Heilemann, M., and Kräusslich, H.-G. (2013) Super-resolution microscopy reveals specific recruitment of HIV-1 envelope proteins to viral assembly sites dependent on the envelope C-terminal tail. PLoS Pathog 9: e1003198.
48. Nebl, T., Pestonjamasp, K.N., Leszyk, J.D., Crowley, J.L., Oh, S.W., and Luna, E.J. (2002) Proteomic analysis of a detergent-resistant membrane skeleton from neutrophil plasma membranes. J Biol Chem 277: 43399-43409.
49. Nguyen, D.H., and Hildreth, J.E. (2000) Evidence for budding of human immunodeficiency virus type 1 selectively from glycolipid-enriched membrane lipid rafts. J Virol 74: 3264- 3272.
50. Ohno, H., Fournier, M.C., Poy, G., and Bonifacino, J.S. (1996) Structural determinants of interaction of tyrosinebased sorting signals with the adaptor medium chains. J Biol Chem 271: 29009-29015.
51. Ohno, H., Aguilar, R.C., Fournier, M.C., Hennecke, S., Cosson, P., and Bonifacino, J.S. (1997) Interaction of endocytic signals from the HIV-1 envelope glycoprotein complex with members of the adaptor medium chain family. Virology 238: 305-315.
52. Ono, A., and Freed, E.O. (2001) Plasma membrane rafts play a critical role in HIV-1 assembly and release. Proc Natl Acad Sci USA 98: 13925-13930.
53. Owen, D.M., Magenau, A., Williamson, D., and Gaus, K. (2012) The lipid raft hypothesis revisited-new insights on raft composition and function from super-resolution fluorescence microscopy. Bioessays 34: 739-747.
54. Popik, W., Alce, T.M., and Au, W. (2002) Human immunodeficiency virus type 1 uses lipid raft-colocalized CD4 and chemokine receptors for productive entry into CD4 ? T cells. J Virol 76: 4709-4722.
55. Poumbourios, P., el Ahmar, W., McPhee, D.A., and Kemp, B.E. (1995) Determinants of human immunodeficiency virus type 1 envelope glycoprotein oligomeric structure. J Virol 69: 1209-1218.
56. Resh, M.D. (2004) Membrane targeting of lipid modified signal transduction proteins. Subcell Biochem 37: 217- 232.
57. Resh, M.D. (2006) Palmitoylation of ligands, receptors, and intracellular signaling molecules. Sci STKE 2006: re14.
58. Rivinoja, A., Hassinen, A., Kokkonen, N., Kauppila, A., and Kellokumpu, S. (2009) Elevated Golgi pH impairs terminal N-glycosylation by inducing mislocalization of Golgi glycosyltransferases. J Cell Physiol 220: 144-154.
59. Rousso, I., Mixon, M.B., Chen, B.K., and Kim, P.S. (2000) Palmitoylation of the HIV-1 envelope glycoprotein is critical for viral infectivity. Proc Natl Acad Sci USA 97: 13523- 13525.
60. Rowell, J.F., Stanhope, P.E., and Siliciano, R.F. (1995) Endocytosis of endogenously synthesized HIV-1 envelope protein. J Immunol 155: 473-488.
61. Roy, N.H., Chan, J., Lambelé, M., and Thali, M. (2013) Clustering and mobility of HIV-1 Env at viral assembly sites predict its propensity to induce cell-cell fusion. J Virol 87: 7516-7525.
62. Salzwedel, K., West, J.T., and Hunter, E. (1999) A conserved tryptophan-rich motif in the membrane-proximal region of the human immunodeficiency virus type 1 gp41 ectodomain is important for Env-mediated fusion and virus infectivity. J Virol 73: 2469-2480.
63. Sanchez, S.A., Tricerri, M.A., and Gratton, E. (2012) Laurdan generalized polarization fluctuations measures membrane packing micro-heterogeneity in vivo. Proc Natl Acad Sci USA 109: 7314-7319.
64. Schweizer, A., Fransen, J.A., Bächi, T., Ginsel, L., and Hauri, H.P. (1988) Identification, by a monoclonal antibody, of a 53-kD protein associated with a tubulo-vesicular compartment at the cis-side of the Golgi apparatus. J Cell Biol 107: 1643-1653.
65. Scolari, S., Engel, S., Krebs, N., Plazzo, A.P., De Almeida, R.F.M., Prieto, M., et al. (2009) Lateral distribution of the transmembrane domain of influenza virus hemagglutinin revealed by time-resolved fluorescence imaging. J Biol Chem 284: 15708-15716.
66. Seifert, M.H.J., Ksiazek, D., Azim, M.K., Smialowski, P., Budisa, N., and Holak, T.A. (2002) Slow exchange in the chromophore of a green fluorescent protein variant. J Am Chem Soc 124: 7932-7942.
67. Sharma, P., Varma, R., Sarasij, R.C., Ira, Gousset, K., Krishnamoorthy, G., et al. (2004) Nanoscale organization of multiple GPI-anchored proteins in living cell membranes. Cell 116: 577-589.
68. Silvius, J.R. (2005) Partitioning of membrane molecules between raft and non-raft domains: insights from modelmembrane studies. Biochim Biophys Acta 1746: 193- 202.
69. Silvius, J.R., and Nabi, I.R. (2006) Fluorescence-quenching and resonance energy transfer studies of lipid microdomains in model and biological membranes. Mol Membr Biol 23: 5-16.
70. Simons, K., and Ikonen, E. (1997) Functional rafts in cell membranes. Nature 387: 569-572.
71. Simons, K., and Sampaio, J.L. (2011) Membrane organization and lipid rafts. Cold Spring Harb Perspect Biol 3: a004697.
72. Snijder, B., Sacher, R., Rämö, P., Damm, E.-M., Liberali, P., and Pelkmans, L. (2009) Population context determines cell-to-cell variability in endocytosis and virus infection. Nature 461: 520-523.
73. Sodroski, J., Goh, W.C., Rosen, C., Campbell, K., and Haseltine, W.A. (1986) Role of the HTLV-III/LAV envelope in syncytium formation and cytopathicity. Nature 322: 470- 474.
74. Somasundaran, M., and Robinson, H.L. (1987) A major mechanism of human immunodeficiency virus-induced cell killing does not involve cell fusion. J Virol 61: 3114-3119.
75. Sugimoto, Y., Ninomiya, H., Ohsaki, Y., Higaki, K., Davies, J.P., Ioannou, Y.A., and Ohno, K. (2001) Accumulation of cholera toxin and GM1 ganglioside in the early endosome of Niemann-Pick C1-deficient cells. Proc Natl Acad Sci USA 98: 12391-12396.
76. Surma, M.A., Klose, C., and Simons, K. (2012) Lipiddependent protein sorting at the trans-Golgi network. Biochim Biophys Acta 1821: 1059-1067.
77. Thompson, R.J., Akana, H.C.S.R., Finnigan, C., Howell, K.E., and Caldwell, J.H. (2006) Anion channels transport ATP into the Golgi lumen. Am J Physiol Cell Physiol 290: C499- C514.
78. Varma, R., and Mayor, S. (1998) GPI-anchored proteins are organized in submicron domains at the cell surface. Nature 394: 798-801.
79. Veillette, M., Désormeaux, A., Medjahed, H., Gharsallah, N.-E., Coutu, M., Baalwa, J., et al. (2013) Interaction with cellular CD4 exposes HIV-1 envelope epitopes targeted by antibody-dependent cell-mediated cytotoxicity. J Virol 88: 2633-2644.
80. Veit, M. (2012) Palmitoylation of virus proteins. Biol Cell 104: 493-515.
81. Vetrivel, K.S., Cheng, H., Lin, W., Sakurai, T., Li, T., Nukina, N., et al. (2004) Association of gamma-secretase with lipid rafts in post-Golgi and endosome membranes. J Biol Chem 279: 44945-44954.
82. Villoing, A., Ridhoir, M., Cinquin, B., Erard, M., Alvarez, L., Vallverdu, G., et al. (2008) Complex fluorescence of the cyan fluorescent protein: comparisons with the H148D variant and consequences for quantitative cell imaging. Biochemistry 47: 12483-12492.
83. Vincent, N., Genin, C., and Malvoisin, E. (2002) Identification of a conserved domain of the HIV-1 transmembrane protein gp41 which interacts with cholesteryl groups. Biochim Biophys Acta 1567: 157-164.
84. Wan, J., Roth, A.F., Bailey, A.O., and Davis, N.G. (2007) Palmitoylated proteins: purification and identification. Nat Protoc 2: 1573-1584.
85. Wyatt, R., and Sodroski, J. (1998) The HIV-1 envelope glycoproteins: fusogens, antigens, and immunogens. Science 280: 1884-1888.
86. Wyss, S., Berlioz-Torrent, C., Boge, M., Blot, G., Höning, S., Benarous, R., and Thali, M. (2001) The highly conserved C-terminal dileucine motif in the cytosolic domain of the human immunodeficiency virus type 1 envelope glycoprotein is critical for its association with the AP-1 clathrin adaptor [correction of adapter]. J Virol 75: 2982-2992.
87. Yang, C., Spies, C.P., and Compans, R.W. (1995) The human and simian immunodeficiency virus envelope glycoprotein transmembrane subunits are palmitoylated. Proc Natl Acad Sci USA 92: 9871-9875.
88. Yang, P., Ai, L.-S., Huang, S.-C., Li, H.-F., Chan, W.-E., Chang, C.-W., et al. (2010) The cytoplasmic domain of human immunodeficiency virus type 1 transmembrane protein gp41 harbors lipid raft association determinants. J Virol 84: 59-75.
89. Yu, X., Yuan, X., McLane, M., Lee, T., and Essex, M. (1993) Mutations in the cytoplasmic domain of human immunodeficiency virus type 1 transmembrane protein impair the incorporation of Env proteins into mature virions. J Virol 19: 505-510.
90. Yuste, E., Johnson, W., Pavlakis, G.N., and Desrosiers, R.C. (2005) Virion envelope content, infectivity, and neutralization sensitivity of simian immunodeficiency virus. J Virol 79: 12455-12463.
91. Zacharias, D.A., Violin, J.D., Newton, A.C., and Tsien, R.Y. (2002) Partitioning of lipid-modified monomeric GFPs into membrane microdomains of live cells. Science 296: 913- 916.
92. Zheng, Y.-H., Plemenitas, A., Fielding, C.J., and Peterlin, B.M. (2003) Nef increases the synthesis of and transports cholesterol to lipid rafts and HIV-1 progeny virions. Proc Natl Acad Sci USA 100: 8460-8465.
93. Zheng, Y.H., Plemenitas, A., Linnemann, T., Fackler, O.T., and Peterlin, B.M. (2001) Nef increases infectivity of HIV via lipid rafts. Curr Biol 11: 875-879.