Remodeling of the host cell plasma membrane by HIV-1 nef and Vpu: A strategy to ensure viral fitness and persistence

Viruses

Volumn 8, Issue 3, 2016, Pages

  Sugden, Scott M ^a   Bego, Mariana G ^a   Pham, Tram N Q ^a   Cohen, Éric A ^a,b  

^a CLIN RESEARCH INSTITUTE OF MONTREAL   (Canada)

^b UNIVERSITÉ DE MONTRÉAL   (Canada)

Author keywords

HIV 1; Host cell surface proteins; Immune evasion; Nef; Replication; Vpu

Indexed keywords

ARALKYLAMINE ACETYLTRANSFERASE; BONE MARROW STROMAL CELL ANTIGEN 2; CELL ANTIGEN; CHEMOKINE RECEPTOR CCR7; ESCRT PROTEIN; HLA A ANTIGEN; HLA B ANTIGEN; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERFERON; L SELECTIN; NEF PROTEIN; PROTEIN; SERINE INCORPORATOR 3; TETRASPANIN; UNCLASSIFIED DRUG; VIRUS GLYCOPROTEIN; VPU PROTEIN; HUMAN IMMUNODEFICIENCY VIRUS PROTEIN; MEMBRANE PROTEIN; NEF PROTEIN, HUMAN IMMUNODEFICIENCY VIRUS 1; VIRAL PROTEIN; VPU PROTEIN, HUMAN IMMUNODEFICIENCY VIRUS 1;

ADAPTIVE IMMUNITY; ANTIBODY DEPENDENT CELLULAR CYTOTOXICITY; ANTIGEN PRESENTING CELL; CD4+ T LYMPHOCYTE; CELL MEMBRANE; ENDOPLASMIC RETICULUM ASSOCIATED DEGRADATION; HUMAN IMMUNODEFICIENCY VIRUS 1; INNATE IMMUNITY; MAJOR HISTOCOMPATIBILITY COMPLEX; NATURAL KILLER T CELL; PLASMACYTOID DENDRITIC CELL; REVIEW; HOST PATHOGEN INTERACTION; METABOLISM; PHYSIOLOGY;

CELL MEMBRANE; HIV-1; HOST-PATHOGEN INTERACTIONS; HUMAN IMMUNODEFICIENCY VIRUS PROTEINS; MEMBRANE PROTEINS; NEF GENE PRODUCTS, HUMAN IMMUNODEFICIENCY VIRUS; VIRAL REGULATORY AND ACCESSORY PROTEINS;

EID: 84960129732     PISSN: None     EISSN: 19994915     Source Type: Journal    
DOI: 10.3390/v8030067     Document Type: Review

References (177)

1. Goldberg, D.M.; Riordan, J.R. Role of membranes in disease. Clin. Physiol. Biochem. 1986, 4, 305–336.
2. Ashrafuzzaman, M.; Tuszynski, J. Membrane-Related Diseases. In Membrane Biophysics; Springer Berlin Heidelberg: Berlin/Heidelberg, Germany, 2012; pp. 151–170.
3. Maartens, G.; Celum, C.; Lewin, S.R. HIV infection: Epidemiology, pathogenesis, treatment, and prevention. Lancet 2014, 384, 258–271.
4. Keele, B.F.; Giorgi, E.E.; Salazar-Gonzalez, J.F.; Decker, J.M.; Pham, K.T.; Salazar, M.G.; Sun, C.; Grayson, T.; Wang, S.; Li, H.; et al. Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection. Proc. Natl. Acad. Sci. USA 2008, 105, 7552–7557.
5. Salazar-Gonzalez, J.F.; Salazar, M.G.; Keele, B.F.; Learn, G.H.; Giorgi, E.E.; Li, H.; Decker, J.M.; Wang, S.; Baalwa, J.; Kraus, M.H.; et al. Genetic identity, biological phenotype, and evolutionary pathways of transmitted/founder viruses in acute and early HIV-1 infection. J. Exp. Med. 2009, 206, 1273–1289.
6. Keele, B.F.; Li, H.; Learn, G.H.; Hraber, P.; Giorgi, E.E.; Grayson, T.; Sun, C.; Chen, Y.; Yeh, W.W.; Letvin, N.L.; et al. Low-dose rectal inoculation of rhesus macaques by SIVsmE660 or SIVmac251 recapitulates human mucosal infection by HIV-1. J. Exp. Med. 2009, 206, 1117–1134.
7. Miller, C.J.; Li, Q.; Abel, K.; Kim, E.Y.; Ma, Z.M.; Wietgrefe, S.; La Franco-Scheuch, L.; Compton, L.; Duan, L.; Shore, M.D.; et al. Propagation and dissemination of infection after vaginal transmission of simian immunodeficiency virus. J. Virol. 2005, 79, 9217–9227.
8. Haase, A.T. Early events in sexual transmission of HIV and SIV and opportunities for interventions. Annu. Rev. Med. 2011, 62, 127–139.
9. Allan, J.S.; Coligan, J.E.; Lee, T.H.; McLane, M.F.; Kanki, P.J.; Groopman, J.E.; Essex, M. A new HTLV-III/LAV encoded antigen detected by antibodies from AIDS patients. Science 1985, 230, 810–813.
10. Deacon, N.J.; Tsykin, A.; Solomon, A.; Smith, K.; Ludford-Menting, M.; Hooker, D.J.; McPhee, D.A.; Greenway, A.L.; Ellett, A.; Chatfield, C.; et al. Genomic structure of an attenuated quasi species of HIV-1 from a blood transfusion donor and recipients. Science 1995, 270, 988–991.
11. Kirchhoff, F.; Greenough, T.C.; Brettler, D.B.; Sullivan, J.L.; Desrosiers, R.C. Brief report: Absence of intact nef sequences in a long-term survivor with nonprogressive HIV-1 infection. N. Engl. J. Med. 1995, 332, 228–232.
12. Kestler, H.W., 3rd; Ringler, D.J.; Mori, K.; Panicali, D.L.; Sehgal, P.K.; Daniel, M.D.; Desrosiers, R.C. Importance of the nef gene for maintenance of high virus loads and for development of AIDS. Cell 1991, 65, 651–662.
13. Liu, L.X.; Heveker, N.; Fackler, O.T.; Arold, S.; Le Gall, S.; Janvier, K.; Peterlin, B.M.; Dumas, C.; Schwartz, O.; Benichou, S.; et al. Mutation of a conserved residue (D123) required for oligomerization of human immunodeficiency virus type 1 Nef protein abolishes interaction with human thioesterase and results in impairment of Nef biological functions. J. Virol. 2000, 74, 5310–5319.
14. Wan, L.; Molloy, S.S.; Thomas, L.; Liu, G.; Xiang, Y.; Rybak, S.L.; Thomas, G. PACS-1 defines a novel gene family of cytosolic sorting proteins required for trans-Golgi network localization. Cell 1998, 94, 205–216.
15. Piguet, V.; Wan, L.; Borel, C.; Mangasarian, A.; Demaurex, N.; Thomas, G.; Trono, D. HIV-1 Nef protein binds to the cellular protein PACS-1 to downregulate class I major histocompatibility complexes. Nat. Cell. Biol. 2000, 2, 163–167.
16. Saksela, K.; Cheng, G.; Baltimore, D. Proline-rich (PxxP) motifs in HIV-1 Nef bind to SH3 domains of a subset of Src kinases and are required for the enhanced growth of Nef+ viruses but not for down-regulation of CD4. EMBO J. 1995, 14, 484–491.
17. Piguet, V.; Gu, F.; Foti, M.; Demaurex, N.; Gruenberg, J.; Carpentier, J.L.; Trono, D. Nef-induced CD4 degradation: A diacidic-based motif in Nef functions as a lysosomal targeting signal through the binding of beta-COP in endosomes. Cell 1999, 97, 63–73.
18. Schwartz, S.; Felber, B.K.; Fenyo, E.M.; Pavlakis, G.N. Env and Vpu proteins of human immunodeficiency virus type 1 are produced from multiple bicistronic mRNAs. J. Virol. 1990, 64, 5448–5456.
19. Pacyniak, E.; Gomez, M.L.; Gomez, L.M.; Mulcahy, E.R.; Jackson, M.; Hout, D.R.; Wisdom, B.J.; Stephens, E.B. Identification of a region within the cytoplasmic domain of the subtype B Vpu protein of human immunodeficiency virus type 1 (HIV-1) that is responsible for retention in the golgi complex and its absence in the Vpu protein from a subtype C HIV-1. AIDS Res. Hum. Retrovir. 2005, 21, 379–394.
20. Schubert, U.; Henklein, P.; Boldyreff, B.; Wingender, E.; Strebel, K.; Porstmann, T. The human immunodeficiency virus type 1 encoded Vpu protein is phosphorylated by casein kinase-2 (CK-2) at positions Ser52 and Ser56 within a predicted alpha-helix-turn-alpha-helix-motif. J. Mol. Biol. 1994, 236, 16–25.
21. Margottin, F.; Bour, S.P.; Durand, H.; Selig, L.; Benichou, S.; Richard, V.; Thomas, D.; Strebel, K.; Benarous, R. A novel human WD protein, h-beta TrCp, that interacts with HIV-1 Vpu connects CD4 to the ER degradation pathway through an F-box motif. Mol. Cell 1998, 1, 565–574.
22. Cohen, E.A.; Terwilliger, E.F.; Sodroski, J.G.; Haseltine, W.A. Identification of a protein encoded by the Vpu gene of HIV-1. Nature 1988, 334, 532–534.
23. Strebel, K.; Klimkait, T.; Martin, M.A. A novel gene of HIV-1, Vpu, and its 16-kilodalton product. Science 1988, 241, 1221–1223.
24. Hout, D.R.; Gomez, M.L.; Pacyniak, E.; Gomez, L.M.; Inbody, S.H.; Mulcahy, E.R.; Culley, N.; Pinson, D.M.; Powers, M.F.; Wong, S.W.; et al. Scrambling of the amino acids within the transmembrane domain of Vpu results in a simian-human immunodeficiency virus (SHIVTM) that is less pathogenic for pig-tailed macaques. Virology 2005, 339, 56–69.
25. Sato, K.; Misawa, N.; Fukuhara, M.; Iwami, S.; An, D.S.; Ito, M.; Koyanagi, Y. Vpu augments the initial burst phase of HIV-1 propagation and downregulates BST2 and CD4 in humanized mice. J. Virol. 2012, 86, 5000–5013.
26. Dave, V.P.; Hajjar, F.; Dieng, M.M.; Haddad, E.; Cohen, E.A. Efficient BST2 antagonism by Vpu is critical for early HIV-1 dissemination in humanized mice. Retrovirology 2013, 10, 128.
27. Willey, R.L.; Maldarelli, F.; Martin, M.A.; Strebel, K. Human immunodeficiency virus type 1 Vpu protein induces rapid degradation of CD4. J. Virol. 1992, 66, 7193–7200.
28. Guy, B.; Kieny, M.P.; Riviere, Y.; Le Peuch, C.; Dott, K.; Girard, M.; Montagnier, L.; Lecocq, J.P. HIV F/3' orf encodes a phosphorylated GTP-binding protein resembling an oncogene product. Nature 1987, 330, 266–269.
29. Wildum, S.; Schindler, M.; Munch, J.; Kirchhoff, F. Contribution of Vpu, Env, and Nef to CD4 down-modulation and resistance of human immunodeficiency virus type 1-infected T cells to superinfection. J. Virol. 2006, 80, 8047–8059.
30. Willey, R.L.; Maldarelli, F.; Martin, M.A.; Strebel, K. Human immunodeficiency virus type 1 Vpu protein regulates the formation of intracellular gp160-CD4 complexes. J. Virol. 1992, 66, 226–234.
31. Ross, T.M.; Oran, A.E.; Cullen, B.R. Inhibition of HIV-1 progeny virion release by cell-surface CD4 is relieved by expression of the viral Nef protein. Curr. Biol. 1999, 9, 613–621.
32. Smalls-Mantey, A.; Connors, M.; Sattentau, Q.J. Comparative efficiency of HIV-1-infected T cell killing by NK cells, monocytes and neutrophils. PLoS ONE 2013, 8, e74858.
33. Rolland, M.; Edlefsen, P.T.; Larsen, B.B.; Tovanabutra, S.; Sanders-Buell, E.; Hertz, T.; deCamp, A.C.; Carrico, C.; Menis, S.; Magaret, C.A.; et al. Increased HIV-1 vaccine efficacy against viruses with genetic signatures in Env V2. Nature 2012, 490, 417–420.
34. Chung, A.W.; Navis, M.; Isitman, G.; Wren, L.; Silvers, J.; Amin, J.; Kent, S.J.; Stratov, I. Activation of NK cells by ADCC antibodies and HIV disease progression. J. Acquir. Immune Defic. Syndr. 2011, 58, 127–131.
35. Jia, M.; Li, D.; He, X.; Zhao, Y.; Peng, H.; Ma, P.; Hong, K.; Liang, H.; Shao, Y. Impaired natural killer cell-induced antibody-dependent cell-mediated cytotoxicity is associated with human immunodeficiency virus-1 disease progression. Clin. Exp. Immunol. 2013, 171, 107–116.
36. Haynes, B.F.; Gilbert, P.B.; McElrath, M.J.; Zolla-Pazner, S.; Tomaras, G.D.; Alam, S.M.; Evans, D.T.; Montefiori, D.C.; Karnasuta, C.; Sutthent, R.; et al. Immune-correlates analysis of an HIV-1 vaccine efficacy trial. N. Engl. J. Med. 2012, 366, 1275–1286.
37. Yates, N.L.; Liao, H.X.; Fong, Y.; Decamp, A.; Vandergrift, N.A.; Williams, W.T.; Alam, S.M.; Ferrari, G.; Yang, Z.Y.; Seaton, K.E.; et al. Vaccine-Induced Env V1-V2 IgG3 Correlates with Lower HIV-1 Infection Risk and Declines Soon After Vaccination. Sci. Transl. Med. 2014, 6, 228ra39.
38. Ferrari, G.; Pollara, J.; Kozink, D.; Harms, T.; Drinker, M.; Freel, S.; Moody, M.A.; Alam, S.M.; Tomaras, G.D.; Ochsenbauer, C.; et al. An HIV-1 gp120 envelope human monoclonal antibody that recognizes a C1 conformational epitope mediates potent antibody-dependent cellular cytotoxicity (ADCC) activity and defines a common ADCC epitope in human HIV-1 serum. J. Virol. 2011, 85, 7029–7036.
39. Bonsignori, M.; Pollara, J.; Moody, M.A.; Alpert, M.D.; Chen, X.; Hwang, K.K.; Gilbert, P.B.; Huang, Y.; Gurley, T.C.; Kozink, D.M.; et al. Antibody-dependent cellular cytotoxicity-mediating antibodies from an HIV-1 vaccine efficacy trial target multiple epitopes and preferentially use the VH1 gene family. J. Virol. 2012, 86, 11521–11532.
40. Wyatt, R.; Moore, J.; Accola, M.; Desjardin, E.; Robinson, J.; Sodroski, J. Involvement of the V1/V2 variable loop structure in the exposure of human immunodeficiency virus type 1 gp120 epitopes induced by receptor binding. J. Virol. 1995, 69, 5723–5733.
41. Veillette, M.; Coutu, M.; Richard, J.; Batraville, L.A.; Dagher, O.; Bernard, N.; Tremblay, C.; Kaufmann, D.E.; Roger, M.; Finzi, A. The HIV-1 gp120 CD4-bound conformation is preferentially targeted by antibody-dependent cellular cytotoxicity-mediating antibodies in sera from HIV-1-infected individuals. J. Virol. 2015, 89, 545–551.
42. Guan, Y.; Pazgier, M.; Sajadi, M.M.; Kamin-Lewis, R.; Al-Darmarki, S.; Flinko, R.; Lovo, E.; Wu, X.; Robinson, J.E.; Seaman, M.S.; et al. Diverse specificity and effector function among human antibodies to HIV-1 envelope glycoprotein epitopes exposed by CD4 binding. Proc. Natl. Acad. Sci. USA 2013, 110, E69–E78.
43. Pham, T.N.; Lukhele, S.; Hajjar, F.; Routy, J.P.; Cohen, E.A. HIV Nef and Vpu protect HIV-infected CD4+ T cells from antibody-mediated cell lysis through down-modulation of CD4 and BST2. Retrovirology 2014, 11, 15.
44. Veillette, M.; Desormeaux, A.; Medjahed, H.; Gharsallah, N.E.; Coutu, M.; Baalwa, J.; Guan, Y.; Lewis, G.; Ferrari, G.; Hahn, B.H.; et al. Interaction with cellular CD4 exposes HIV-1 envelope epitopes targeted by antibody-dependent cell-mediated cytotoxicity. J. Virol. 2014, 88, 2633–2644.
45. Grzesiek, S.; Stahl, S.J.; Wingfield, P.T.; Bax, A. The CD4 determinant for downregulation by HIV-1 Nef directly binds to Nef. Mapping of the Nef binding surface by NMR. Biochemistry 1996, 35, 10256–10261.
46. Preusser, A.; Briese, L.; Baur, A.S.; Willbold, D. Direct in vitro binding of full-length human immunodeficiency virus type 1 Nef protein to CD4 cytoplasmic domain. J. Virol. 2001, 75, 3960–3964.
47. Chaudhuri, R.; Lindwasser, O.W.; Smith, W.J.; Hurley, J.H.; Bonifacino, J.S. Downregulation of CD4 by human immunodeficiency virus type 1 Nef is dependent on clathrin and involves direct interaction of Nef with the AP2 clathrin adaptor. J. Virol. 2007, 81, 3877–3890.
48. Lindwasser, O.W.; Smith, W.J.; Chaudhuri, R.; Yang, P.; Hurley, J.H.; Bonifacino, J.S. A diacidic motif in human immunodeficiency virus type 1 Nef is a novel determinant of binding to AP-2. J. Virol. 2008, 82, 1166–1174.
49. Schaefer, M.R.; Wonderlich, E.R.; Roeth, J.F.; Leonard, J.A.; Collins, K.L. HIV-1 Nef targets MHC-I and CD4 for degradation via a final common beta-COP-dependent pathway in T cells. PLoS Pathog. 2008, 4, e1000131.
50. DaSilva, L.L.; Sougrat, R.; Burgos, P.V.; Janvier, K.; Mattera, R.; Bonifacino, J.S. Human immunodeficiency virus type 1 Nef protein targets CD4 to the multivesicular body pathway. J. Virol. 2009, 83, 6578–6590.
51. Schubert, U.; Anton, L.C.; Bacik, I.; Cox, J.H.; Bour, S.; Bennink, J.R.; Orlowski, M.; Strebel, K.; Yewdell, J.W. CD4 glycoprotein degradation induced by human immunodeficiency virus type 1 Vpu protein requires the function of proteasomes and the ubiquitin-conjugating pathway. J. Virol. 1998, 72, 2280–2288.
52. Binette, J.; Dube, M.; Mercier, J.; Halawani, D.; Latterich, M.; Cohen, E.A. Requirements for the selective degradation of CD4 receptor molecules by the human immunodeficiency virus type 1 Vpu protein in the endoplasmic reticulum. Retrovirology 2007, 4, 75.
53. Magadan, J.G.; Perez-Victoria, F.J.; Sougrat, R.; Ye, Y.; Strebel, K.; Bonifacino, J.S. Multilayered mechanism of CD4 downregulation by HIV-1 Vpu involving distinct ER retention and ERAD targeting steps. PLoS Pathog. 2010, 6, e1000869.
54. Mohammadi, P.; Desfarges, S.; Bartha, I.; Joos, B.; Zangger, N.; Munoz, M.; Gunthard, H. F.; Beerenwinkel, N.; Telenti, A.; Ciuffi, A. 24 hours in the life of HIV-1 in a T cell line. PLoS Pathog. 2013, 9, e1003161.
55. Yao, X.J.; Friborg, J.; Checroune, F.; Gratton, S.; Boisvert, F.; Sekaly, R.P.; Cohen, E.A. Degradation of CD4 induced by human immunodeficiency virus type 1 Vpu protein: A predicted alpha-helix structure in the proximal cytoplasmic region of CD4 contributes to Vpu sensitivity. Virology 1995, 209, 615–623.
56. Bour, S.; Schubert, U.; Strebel, K. The human immunodeficiency virus type 1 Vpu protein specifically binds to the cytoplasmic domain of CD4: Implications for the mechanism of degradation. J. Virol. 1995, 69, 1510–1520.
57. Bour, S.; Strebel, K. The HIV-1 Vpu protein: A multifunctional enhancer of viral particle release. Microbes Infect. 2003, 5, 1029–1039.
58. Neil, S.J.; Eastman, S.W.; Jouvenet, N.; Bieniasz, P.D. HIV-1 Vpu promotes release and prevents endocytosis of nascent retrovirus particles from the plasma membrane. PLoS Pathog. 2006, 2, e39.
59. Geraghty, R.J.; Talbot, K.J.; Callahan, M.; Harper, W.; Panganiban, A.T. Cell type-dependence for Vpu function. J. Med. Primatol. 1994, 23, 146–150.
60. Varthakavi, V.; Smith, R.M.; Bour, S.P.; Strebel, K.; Spearman, P. Viral protein U counteracts a human host cell restriction that inhibits HIV-1 particle production. Proc. Natl. Acad. Sci. USA 2003, 100, 15154–15159.
61. Neil, S.J.; Sandrin, V.; Sundquist, W.I.; Bieniasz, P.D. An interferon-alpha-induced tethering mechanism inhibits HIV-1 and Ebola virus particle release but is counteracted by the HIV-1 Vpu protein. Cell Host Microbe 2007, 2, 193–203.
62. Van Damme, N.; Goff, D.; Katsura, C.; Jorgenson, R.L.; Mitchell, R.; Johnson, M.C.; Stephens, E.B.; Guatelli, J. The interferon-induced protein BST-2 restricts HIV-1 release and is downregulated from the cell surface by the viral Vpu protein. Cell Host Microbe 2008, 3, 245–252.
63. Neil, S.J.; Zang, T.; Bieniasz, P.D. Tetherin inhibits retrovirus release and is antagonized by HIV-1 Vpu. Nature 2008, 451, 425–430.
64. Arias, J.F.; Iwabu, Y.; Tokunaga, K. Structural Basis for the Antiviral Activity of BST-2/Tetherin and Its Viral Antagonism. Front. Microbiol. 2011, 2, 250.
65. Hinz, A.; Miguet, N.; Natrajan, G.; Usami, Y.; Yamanaka, H.; Renesto, P.; Hartlieb, B.; McCarthy, A.A.; Simorre, J.P.; Gottlinger, H.; et al. Structural basis of HIV-1 tethering to membranes by the BST-2/tetherin ectodomain. Cell Host Microbe 2010, 7, 314–323.
66. Schubert, H.L.; Zhai, Q.; Sandrin, V.; Eckert, D.M.; Garcia-Maya, M.; Saul, L.; Sundquist, W.I.; Steiner, R.A.; Hill, C.P. Structural and functional studies on the extracellular domain of BST2/tetherin in reduced and oxidized conformations. Proc. Natl. Acad. Sci. USA 2010, 107, 17951–17956.
67. Venkatesh, S.; Bieniasz, P.D. Mechanism of HIV-1 virion entrapment by tetherin. PLoS Pathog. 2013, 9, e1003483.
68. Perez-Caballero, D.; Zang, T.; Ebrahimi, A.; McNatt, M.W.; Gregory, D.A.; Johnson, M.C.; Bieniasz, P.D. Tetherin inhibits HIV-1 release by directly tethering virions to cells. Cell 2009, 139, 499–511.
69. Lehmann, M.; Rocha, S.; Mangeat, B.; Blanchet, F.; Uji, I.H.; Hofkens, J.; Piguet, V. Quantitative multicolor super-resolution microscopy reveals tetherin HIV-1 interaction. PLoS Pathog. 2011, 7, e1002456.
70. Miyagi, E.; Andrew, A.J.; 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. USA 2009, 106, 2868–2873.
71. Dube, M.; Roy, B.B.; Guiot-Guillain, P.; Binette, J.; Mercier, J.; Chiasson, A.; Cohen, E.A. Antagonism of tetherin restriction of HIV-1 release by Vpu involves binding and sequestration of the restriction factor in a perinuclear compartment. PLoS Pathog. 2010, 6, e1000856.
72. McNatt, M.W.; Zang, T.; Bieniasz, P.D. Vpu Binds Directly to Tetherin and Displaces It from Nascent Virions. PLoS Pathog. 2013, 9, e1003299.
73. Vigan, R.; Neil, S.J. Determinants of tetherin antagonism in the transmembrane domain of the human immunodeficiency virus type 1 Vpu protein. J. Virol. 2010, 84, 12958–12970.
74. Skasko, M.; Wang, Y.; Tian, Y.; Tokarev, A.; Munguia, J.; Ruiz, A.; Stephens, E.B.; Opella, S.J.; Guatelli, J. HIV-1 Vpu protein antagonizes innate restriction factor BST-2 via lipid-embedded helix-helix interactions. J. Biol. Chem. 2012, 287, 58–67.
75. Janvier, K.; Pelchen-Matthews, A.; Renaud, J.B.; Caillet, M.; Marsh, M.; Berlioz-Torrent, C. The ESCRT-0 component HRS is required for HIV-1 Vpu-mediated BST-2/tetherin down-regulation. PLoS Pathog. 2011, 7, e1001265.
76. Douglas, J.L.; Viswanathan, K.; McCarroll, M.N.; Gustin, J.K.; Fruh, K.; Moses, A.V. Vpu directs the degradation of the human immunodeficiency virus restriction factor BST-2/Tetherin via a {beta}TrCP-dependent mechanism. J. Virol. 2009, 83, 7931–7947.
77. Mitchell, R.S.; Katsura, C.; Skasko, M.A.; Fitzpatrick, K.; Lau, D.; Ruiz, A.; Stephens, E.B.; Margottin-Goguet, F.; Benarous, R.; Guatelli, J.C. Vpu antagonizes BST-2-mediated restriction of HIV-1 release via beta-TrCP and endo-lysosomal trafficking. PLoS Pathog. 2009, 5, e1000450.
78. Tokarev, A.A.; Munguia, J.; Guatelli, J.C. Serine-threonine ubiquitination mediates downregulation of BST-2/tetherin and relief of restricted virion release by HIV-1 Vpu. J. Virol. 2011, 85, 51–63.
79. Gustin, J.K.; Douglas, J.L.; Bai, Y.; Moses, A.V. Ubiquitination of BST-2 protein by HIV-1 Vpu protein does not require lysine, serine, or threonine residues within the BST-2 cytoplasmic domain. J. Biol. Chem. 2012, 287, 14837–14850.
80. Tervo, H.M.; Homann, S.; Ambiel, I.; Fritz, J.V.; Fackler, O.T.; Keppler, O.T. beta-TrCP is dispensable for Vpu's ability to overcome the CD317/Tetherin-imposed restriction to HIV-1 release. Retrovirology 2011, 8, 9.
81. Schmidt, S.; Fritz, J.V.; Bitzegeio, J.; Fackler, O.T.; Keppler, O.T. HIV-1 Vpu blocks recycling and biosynthetic transport of the intrinsic immunity factor CD317/tetherin to overcome the virion release restriction. MBio 2011, 2, e00036–11.
82. Kueck, T.; Neil, S.J. A cytoplasmic tail determinant in HIV-1 Vpu mediates targeting of tetherin for endosomal degradation and counteracts interferon-induced restriction. PLoS Pathog. 2012, 8, e1002609.
83. Kueck, T.; Foster, T.L.; Weinelt, J.; Sumner, J.C.; Pickering, S.; Neil, S.J.D. Serine Phosphorylation of HIV-1 Vpu and Its Binding to Tetherin Regulates Interaction with Clathrin Adaptors. PLoS Pathog. 2015, 11, e1005141.
84. Galao, R.P.; Le Tortorec, A.; Pickering, S.; Kueck, T.; Neil, S.J. Innate sensing of HIV-1 assembly by Tetherin induces NFkappaB-dependent proinflammatory responses. Cell Host Microbe 2012, 12, 633–644.
85. Weinelt, J.; Neil, S.J. Differential sensitivities of tetherin isoforms to counteraction by primate lentiviruses. J. Virol. 2014, 88, 5845–5858.
86. Dube, M.; Paquay, C.; Roy, B.B.; Bego, M.G.; Mercier, J.; Cohen, E.A. HIV-1 Vpu antagonizes BST-2 by interfering mainly with the trafficking of newly synthesized BST-2 to the cell surface. Traffic 2011, 12, 1714–1729.
87. Lau, D.; Kwan, W.; Guatelli, J. Role of the endocytic pathway in the counteraction of BST-2 by human lentiviral pathogens. J. Virol. 2011, 85, 9834–9846.
88. Jia, X.; Weber, E.; Tokarev, A.; Lewinski, M.; Rizk, M.; Suarez, M.; Guatelli, J.; Xiong, Y. Structural basis of HIV-1 Vpu-mediated BST2 antagonism via hijacking of the clathrin adaptor protein complex 1. Elife 2014, 3, e02362.
89. Galao, R.P.; Pickering, S.; Curnock, R.; Neil, S.J. Retroviral retention activates a Syk-dependent HemITAM in human tetherin. Cell Host Microbe 2014, 16, 291–303.
90. Cocka, L.J.; Bates, P. Identification of alternatively translated Tetherin isoforms with differing antiviral and signaling activities. PLoS Pathog. 2012, 8, e1002931.
91. Kobayashi, T.; Takeuchi, J.S.; Ren, F.; Matsuda, K.; Sato, K.; Kimura, Y.; Misawa, N.; Yoshikawa, R.; Nakano, Y.; Yamada, E.; et al. Characterization of red-capped mangabey tetherin: Implication for the co-evolution of primates and their lentiviruses. Sci. Rep. 2014, 4, 5529.
92. Colonna, M.; Trinchieri, G.; Liu, Y.J. Plasmacytoid dendritic cells in immunity. Nat. Immunol. 2004, 5, 1219–1226.
93. Lepelley, A.; Louis, S.; Sourisseau, M.; Law, H.K.; Pothlichet, J.; Schilte, C.; Chaperot, L.; Plumas, J.; Randall, R.E.; Si-Tahar, M.; et al. Innate sensing of HIV-infected cells. PLoS Pathog. 2011, 7, e1001284.
94. Fonteneau, J.F.; Larsson, M.; Beignon, A.S.; McKenna, K.; Dasilva, I.; Amara, A.; Liu, Y.J.; Lifson, J.D.; Littman, D.R.; Bhardwaj, N. Human immunodeficiency virus type 1 activates plasmacytoid dendritic cells and concomitantly induces the bystander maturation of myeloid dendritic cells. J. Virol. 2004, 78, 5223–5232.
95. Beignon, A.S.; McKenna, K.; Skoberne, M.; Manches, O.; DaSilva, I.; Kavanagh, D.G.; Larsson, M.; Gorelick, R.J.; Lifson, J.D.; Bhardwaj, N. Endocytosis of HIV-1 activates plasmacytoid dendritic cells via Toll-like receptor-viral RNA interactions. J. Clin. Investig. 2005, 115, 3265–3275.
96. Cao, W.; Bover, L.; Cho, M.; Wen, X.; Hanabuchi, S.; Bao, M.; Rosen, D.B.; Wang, Y.H.; Shaw, J.L.; Du, Q.; et al. Regulation of TLR7/9 responses in plasmacytoid dendritic cells by BST2 and ILT7 receptor interaction. J. Exp. Med. 2009, 206, 1603–1614.
97. Bego, M.G.; Cote, E.; Aschman, N.; Mercier, J.; Weissenhorn, W.; Cohen, E.A. Vpu Exploits the Cross-Talk between BST2 and the ILT7 Receptor to Suppress Anti-HIV-1 Responses by Plasmacytoid Dendritic Cells. PLoS Pathog. 2015, 11, e1005024.
98. Arias, J.F.; Heyer, L.N.; von Bredow, B.; Weisgrau, K.L.; Moldt, B.; Burton, D.R.; Rakasz, E.G.; Evans, D.T. Tetherin antagonism by Vpu protects HIV-infected cells from antibody-dependent cell-mediated cytotoxicity. Proc. Natl. Acad. Sci. USA 2014, 111, 6425–6430.
99. Alvarez, R.A.; Hamlin, R.E.; Monroe, A.; Moldt, B.; Hotta, M.T.; Rodriguez Caprio, G.; Fierer, D.S.; Simon, V.; Chen, B.K. HIV-1 Vpu antagonism of tetherin inhibits antibody-dependent cellular cytotoxic responses by natural killer cells. J. Virol. 2014, 88, 6031–6046.
100. Chowers, M.Y.; Spina, C.A.; Kwoh, T.J.; Fitch, N.J.; Richman, D.D.; Guatelli, J.C. Optimal infectivity in vitro of human immunodeficiency virus type 1 requires an intact nef gene. J. Virol. 1994, 68, 2906–2914.
101. Carl, S.; Greenough, T.C.; Krumbiegel, M.; Greenberg, M.; Skowronski, J.; Sullivan, J.L.; Kirchhoff, F. Modulation of different human immunodeficiency virus type 1 Nef functions during progression to AIDS. J. Virol. 2001, 75, 3657–3665.
102. Aiken, C.; Trono, D. Nef stimulates human immunodeficiency virus type 1 proviral DNA synthesis. J. Virol. 1995, 69, 5048–5056.
103. Pizzato, M.; Helander, A.; Popova, E.; Calistri, A.; Zamborlini, A.; Palu, G.; Gottlinger, H.G. Dynamin 2 is required for the enhancement of HIV-1 infectivity by Nef. Proc. Natl. Acad. Sci. USA 2007, 104, 6812–6817.
104. Luo, T.; Douglas, J.L.; Livingston, R.L.; Garcia, J.V. Infectivity enhancement by HIV-1 Nef is dependent on the pathway of virus entry: Implications for HIV-based gene transfer systems. Virology 1998, 241, 224–233.
105. Pizzato, M.; Popova, E.; Gottlinger, H.G. Nef can enhance the infectivity of receptor-pseudotyped human immunodeficiency virus type 1 particles. J. Virol. 2008, 82, 10811–10819.
106. Miller, M.D.; Warmerdam, M.T.; Page, K.A.; Feinberg, M.B.; Greene, W.C. Expression of the human immunodeficiency virus type 1 (HIV-1) nef gene during HIV-1 production increases progeny particle infectivity independently of gp160 or viral entry. J. Virol. 1995, 69, 579–584.
107. Chazal, N.; Singer, G.; Aiken, C.; Hammarskjold, M.L.; Rekosh, D. Human immunodeficiency virus type 1 particles pseudotyped with envelope proteins that fuse at low pH no longer require Nef for optimal infectivity. J. Virol. 2001, 75, 4014–4018.
108. Rosa, A.; Chande, A.; Ziglio, S.; De Sanctis, V.; Bertorelli, R.; Goh, S.L.; McCauley, S.M.; Nowosielska, A.; Antonarakis, S.E.; Luban, J.; et al. HIV-1 Nef promotes infection by excluding SERINC5 from virion incorporation. Nature 2015, 526, 212–217.
109. Usami, Y.; Wu, Y.; Gottlinger, H.G. SERINC3 and SERINC5 restrict HIV-1 infectivity and are counteracted by Nef. Nature 2015, 526, 218–223.
110. Cohen, F.S.; Melikyan, G.B. The energetics of membrane fusion from binding, through hemifusion, pore formation, and pore enlargement. J. Membr. Biol. 2004, 199, 1–14.
111. Claas, C.; Stipp, C.S.; Hemler, M.E. Evaluation of prototype transmembrane 4 superfamily protein complexes and their relation to lipid rafts. J. Biol. Chem. 2001, 276, 7974–7984.
112. Jolly, C.; Mitar, I.; Sattentau, Q.J. Adhesion molecule interactions facilitate human immunodeficiency virus type 1-induced virological synapse formation between T cells. J. Virol. 2007, 81, 13916–13921.
113. Nydegger, S.; Khurana, S.; Krementsov, D.N.; Foti, M.; Thali, M. Mapping of tetraspanin-enriched microdomains that can function as gateways for HIV-1. J. Cell Biol. 2006, 173, 795–807.
114. Hogue, I.B.; Grover, J.R.; Soheilian, F.; Nagashima, K.; Ono, A. Gag induces the coalescence of clustered lipid rafts and tetraspanin-enriched microdomains at HIV-1 assembly sites on the plasma membrane. J. Virol. 2011, 85, 9749–9766.
115. Symeonides, M.; Lambele, M.; Roy, N.H.; Thali, M. Evidence showing that tetraspanins inhibit HIV-1-induced cell-cell fusion at a post-hemifusion stage. Viruses 2014, 6, 1078–1090.
116. Takeda, Y.; Tachibana, I.; Miyado, K.; Kobayashi, M.; Miyazaki, T.; Funakoshi, T.; Kimura, H.; Yamane, H.; Saito, Y.; Goto, H.; et al. Tetraspanins CD9 and CD81 function to prevent the fusion of mononuclear phagocytes. J. Cell. Biol. 2003, 161, 945–956.
117. Huerta, L.; Lopez-Balderas, N.; Rivera-Toledo, E.; Sandoval, G.; Gomez-Icazbalceta, G.; Villarreal, C.; Lamoyi, E.; Larralde, C. HIV-envelope-dependent cell-cell fusion: Quantitative studies. ScientificWorldJournal 2009, 9, 746–763.
118. Weng, J.; Krementsov, D.N.; Khurana, S.; Roy, N.H.; Thali, M. Formation of syncytia is repressed by tetraspanins in human immunodeficiency virus type 1-producing cells. J. Virol. 2009, 83, 7467–7474.
119. Gordon-Alonso, M.; Yanez-Mo, M.; Barreiro, O.; Alvarez, S.; Munoz-Fernandez, M.A.; Valenzuela-Fernandez, A.; Sanchez-Madrid, F. Tetraspanins CD9 and CD81 modulate HIV-1-induced membrane fusion. J. Immunol. 2006, 177, 5129–5137.
120. Sato, K.; Aoki, J.; Misawa, N.; Daikoku, E.; Sano, K.; Tanaka, Y.; Koyanagi, Y. Modulation of human immunodeficiency virus type 1 infectivity through incorporation of tetraspanin proteins. J. Virol. 2008, 82, 1021–1033.
121. Lambele, M.; Koppensteiner, H.; Symeonides, M.; Roy, N.H.; Chan, J.; Schindler, M.; Thali, M. Vpu Is the Main Determinant for Tetraspanin Downregulation in HIV-1-Infected Cells. J. Virol. 2015, 89, 3247–3255
122. Haller, C.; Muller, B.; Fritz, J.V.; Lamas-Murua, M.; Stolp, B.; Pujol, F.M.; Keppler, O.T.; Fackler, O.T. HIV-1 Nef and Vpu are functionally redundant broad-spectrum modulators of cell surface receptors, including tetraspanins. J. Virol. 2014, 88, 14241–14257.
123. Matheson, N.J.; Sumner, J.; Wals, K.; Rapiteanu, R.; Weekes, M.P.; Vigan, R.; Weinelt, J.; Schindler, M.; Antrobus, R.; Costa, A.S.; et al. Cell Surface Proteomic Map of HIV Infection Reveals Antagonism of Amino Acid Metabolism by Vpu and Nef. Cell Host Microbe 2015, 18, 409–423.
124. Schwartz, O.; Marechal, V.; Le Gall, S.; Lemonnier, F.; Heard, J.M. Endocytosis of major histocompatibility complex class I molecules is induced by the HIV-1 Nef protein. Nat. Med. 1996, 2, 338–342.
125. Collins, K.L.; Chen, B.K.; Kalams, S.A.; Walker, B.D.; Baltimore, D. HIV-1 Nef protein protects infected primary cells against killing by cytotoxic T lymphocytes. Nature 1998, 391, 397–401.
126. Noviello, C.M.; Benichou, S.; Guatelli, J.C. Cooperative binding of the class I major histocompatibility complex cytoplasmic domain and human immunodeficiency virus type 1 Nef to the endosomal AP-1 complex via its mu subunit. J. Virol. 2008, 82, 1249–1258.
127. Jia, X.; Singh, R.; Homann, S.; Yang, H.; Guatelli, J.; Xiong, Y. Structural basis of evasion of cellular adaptive immunity by HIV-1 Nef. Nat. Struct. Mol. Biol. 2012, 19, 701–706.
128. Wonderlich, E.R.; Williams, M.; Collins, K.L. The tyrosine binding pocket in the adaptor protein 1 (AP-1) mu1 subunit is necessary for Nef to recruit AP-1 to the major histocompatibility complex class I cytoplasmic tail. J. Biol. Chem. 2008, 283, 3011–3022.
129. Kasper, M.R.; Roeth, J.F.; Williams, M.; Filzen, T.M.; Fleis, R.I.; Collins, K.L. HIV-1 Nef disrupts antigen presentation early in the secretory pathway. J. Biol. Chem. 2005, 280, 12840–12848.
130. Leonard, J.A.; Filzen, T.; Carter, C.C.; Schaefer, M.; Collins, K.L. HIV-1 Nef disrupts intracellular trafficking of major histocompatibility complex class I, CD4, CD8, and CD28 by distinct pathways that share common elements. J. Virol. 2011, 85, 6867–6881.
131. Hung, C.H.; Thomas, L.; Ruby, C.E.; Atkins, K.M.; Morris, N.P.; Knight, Z.A.; Scholz, I.; Barklis, E.; Weinberg, A.D.; Shokat, K.M.; et al. HIV-1 Nef assembles a Src family kinase-ZAP-70/Syk-PI3K cascade to downregulate cell-surface MHC-I. Cell Host Microbe 2007, 1, 121–133.
132. Atkins, K.M.; Thomas, L.; Youker, R.T.; Harriff, M.J.; Pissani, F.; You, H.; Thomas, G. 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. 2008, 283, 11772–11784.
133. Blagoveshchenskaya, A.D.; Thomas, L.; Feliciangeli, S.F.; Hung, C.H.; Thomas, G. HIV-1 Nef downregulates MHC-I by a PACS-1- and PI3K-regulated ARF6 endocytic pathway. Cell 2002, 111, 853–866.
134. Dikeakos, J.D.; Atkins, K.M.; Thomas, L.; Emert-Sedlak, L.; Byeon, I.J.; Jung, J.; Ahn, J.; Wortman, M.D.; Kukull, B.; Saito, M.; et al. Small molecule inhibition of HIV-1-induced MHC-I down-regulation identifies a temporally regulated switch in Nef action. Mol. Biol. Cell 2010, 21, 3279–3292.
135. Wonderlich, E.R.; Leonard, J.A.; Kulpa, D.A.; Leopold, K.E.; Norman, J.M.; Collins, K.L. ADP ribosylation factor 1 activity is required to recruit AP-1 to the major histocompatibility complex class I (MHC-I) cytoplasmic tail and disrupt MHC-I trafficking in HIV-1-infected primary T cells. J. Virol. 2011, 85, 12216–12226.
136. Yi, L.; Rosales, T.; Rose, J.J.; Chowdhury, B.; Knutson, J.R.; Venkatesan, S. HIV-1 Nef binds a subpopulation of MHC-I throughout its trafficking itinerary and down-regulates MHC-I by perturbing both anterograde and retrograde trafficking. J. Biol. Chem. 2010, 285, 30884–308905.
137. Dikeakos, J.D.; Thomas, L.; Kwon, G.; Elferich, J.; Shinde, U.; Thomas, G. An interdomain binding site on HIV-1 Nef interacts with PACS-1 and PACS-2 on endosomes to down-regulate MHC-I. Mol. Biol. Cell 2012, 23, 2184–2197.
138. Le Gall, S.; Erdtmann, L.; Benichou, S.; Berlioz-Torrent, C.; Liu, L.; Benarous, R.; Heard, J.M.; Schwartz, O. Nef interacts with the mu subunit of clathrin adaptor complexes and reveals a cryptic sorting signal in MHC I molecules. Immunity 1998, 8, 483–495.
139. Cohen, G.B.; Gandhi, R.T.; Davis, D.M.; Mandelboim, O.; Chen, B.K.; Strominger, J.L.; Baltimore, D. The selective downregulation of class I major histocompatibility complex proteins by HIV-1 protects HIV-infected cells from NK cells. Immunity 1999, 10, 661–671.
140. Stumptner-Cuvelette, P.; Morchoisne, S.; Dugast, M.; Le Gall, S.; Raposo, G.; Schwartz, O.; Benaroch, P. HIV-1 Nef impairs MHC class II antigen presentation and surface expression. Proc. Natl. Acad. Sci. USA 2001, 98, 12144–12149.
141. Schindler, M.; Wurfl, S.; Benaroch, P.; Greenough, T.C.; Daniels, R.; Easterbrook, P.; Brenner, M.; Munch, J.; Kirchhoff, F. 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. 2003, 77, 10548–10556.
142. Ghiglione, Y.; Rodriguez, A.M.; De Candia, C.; Carobene, M.; Benaroch, P.; Schindler, M.; Salomon, H.; Turk, G. HIV-mediated up-regulation of invariant chain (CD74) correlates with generalized immune activation in HIV+ subjects. Virus Res. 2012, 163, 380–384.
143. Chaudhry, A.; Verghese, D.A.; Das, S.R.; Jameel, S.; George, A.; Bal, V.; Mayor, S.; Rath, S. HIV-1 Nef promotes endocytosis of cell surface MHC class II molecules via a constitutive pathway. J. Immunol. 2009, 183, 2415–2424.
144. Kadri, N.; Wagner, A.K.; Ganesan, S.; Karre, K.; Wickstrom, S.; Johansson, M.H.; Hoglund, P. Dynamic Regulation of NK Cell Responsiveness. Curr. Top. Microbiol. Immunol. 2015, 395, 95–114.
145. Alter, G.; Altfeld, M. NK cells in HIV-1 infection: Evidence for their role in the control of HIV-1 infection. J. Intern. Med. 2009, 265, 29–42.
146. Luteijn, R.; Sciaranghella, G.; van Lunzen, J.; Nolting, A.; Dugast, A.S.; Ghebremichael, M.S.; Altfeld, M.; Alter, G. Early viral replication in lymph nodes provides HIV with a means by which to escape NK-cell-mediated control. Eur. J. Immunol. 2011, 41, 2729–2740.
147. Cerboni, C.; Neri, F.; Casartelli, N.; Zingoni, A.; Cosman, D.; Rossi, P.; Santoni, A.; Doria, M. Human immunodeficiency virus 1 Nef protein downmodulates the ligands of the activating receptor NKG2D and inhibits natural killer cell-mediated cytotoxicity. J. Gen. Virol. 2007, 88, 242–250.
148. Fausther-Bovendo, H.; Sol-Foulon, N.; Candotti, D.; Agut, H.; Schwartz, O.; Debre, P.; Vieillard, V. HIV escape from natural killer cytotoxicity: Nef inhibits NKp44L expression on CD4+ T cells. AIDS 2009, 23, 1077–1087.
149. Falco, M.; Marcenaro, E.; Romeo, E.; Bellora, F.; Marras, D.; Vely, F.; Ferracci, G.; Moretta, L.; Moretta, A.; Bottino, C. Homophilic interaction of NTBA, a member of the CD2 molecular family: Induction of cytotoxicity and cytokine release in human NK cells. Eur. J. Immunol. 2004, 34, 1663–1672.
150. Shah, A.H.; Sowrirajan, B.; Davis, Z.B.; Ward, J.P.; Campbell, E.M.; Planelles, V.; Barker, E. Degranulation of natural killer cells following interaction with HIV-1-infected cells is hindered by downmodulation of NTB-A by Vpu. Cell Host Microbe 2010, 8, 397–409.
151. Ramirez, P.W.; DePaula-Silva, A.B.; Szaniawski, M.; Barker, E.; Bosque, A.; Planelles, V. HIV-1 Vpu utilizes both cullin-RING ligase (CRL) dependent and independent mechanisms to downmodulate host proteins. Retrovirology 2015, 12, 65.
152. Bolduan, S.; Hubel, P.; Reif, T.; Lodermeyer, V.; Hohne, K.; Fritz, J.V.; Sauter, D.; Kirchhoff, F.; Fackler, O.T.; Schindler, M.; et al. HIV-1 Vpu affects the anterograde transport and the glycosylation pattern of NTB-A. Virology 2013, 440, 190–203.
153. Shibuya, A.; Campbell, D.; Hannum, C.; Yssel, H.; Franz-Bacon, K.; McClanahan, T.; Kitamura, T.; Nicholl, J.; Sutherland, G.R.; Lanier, L.L.; Phillips, J.H. DNAM-1, a novel adhesion molecule involved in the cytolytic function of T lymphocytes. Immunity 1996, 4, 573–581.
154. Matusali, G.; Potesta, M.; Santoni, A.; Cerboni, C.; Doria, M. The human immunodeficiency virus type 1 Nef and Vpu proteins downregulate the natural killer cell-activating ligand PVR. J. Virol. 2012, 86, 4496–4504.
155. Bolduan, S.; Reif, T.; Schindler, M.; Schubert, U. HIV-1 Vpu mediated downregulation of CD155 requires alanine residues 10, 14 and 18 of the transmembrane domain. Virology 2014, 464–465, 375–384.
156. Tupin, E.; Kinjo, Y.; Kronenberg, M. The unique role of natural killer T cells in the response tomicroorganisms. Nat. Rev. Microbiol. 2007, 5, 405–417.
157. Moll, M.; Andersson, S.K.; Smed-Sorensen, A.; Sandberg, J.K. Inhibition of lipid antigen presentation in dendritic cells by HIV-1 Vpu interference with CD1d recycling from endosomal compartments. Blood 2010, 116, 1876–1884.
158. Bachle, S.M.; Sauter, D.; Sibitz, S.; Sandberg, J.K.; Kirchhoff, F.; Moll, M. Involvement of a C-terminal motif in the interference of primate lentiviral Vpu proteins with CD1d-mediated antigen presentation. Sci. Rep. 2015, 5, 9675.
159. Sandberg, J.K.; Andersson, S.K.; Bachle, S.M.; Nixon, D.F.; Moll, M. HIV-1 Vpu interference with innate cell-mediated immune mechanisms. Curr. HIV Res. 2012, 10, 327–333.
160. Cho, S.; Knox, K.S.; Kohli, L.M.; He, J.J.; Exley, M.A.; Wilson, S.B.; Brutkiewicz, R.R. Impaired cell surface expression of human CD1d by the formation of an HIV-1 Nef/CD1d complex. Virology 2005, 337, 242–252.
161. Chen, N.; McCarthy, C.; Drakesmith, H.; Li, D.; Cerundolo, V.; McMichael, A.J.; Screaton, G.R.; Xu, X.N. HIV-1 down-regulates the expression of CD1d via Nef. Eur. J. Immunol. 2006, 36, 278–286.
162. Kelly, H.; Mandraju, R.; Coelho-dos-Reis, J.G.; Tsuji, M. Effects of HIV-1-induced CD1c and CD1d modulation and endogenous lipid presentation on CD1c-restricted T-cell activation. BMC Immunol. 2013, 14, 4
163. Rodionov, D.G.; Nordeng, T.W.; Pedersen, K.; Balk, S.P.; Bakke, O. A critical tyrosine residue in the cytoplasmic tail is important for CD1d internalization but not for its basolateral sorting in MDCK cells. J. Immunol. 1999, 162, 1488–1495.
164. Ly, D.; Moody, D.B. The CD1 size problem: Lipid antigens, ligands, and scaffolds. Cell. Mol. Life Sci. 2014, 71, 3069–3079.
165. Ramirez, P.W.; Famiglietti, M.; Sowrirajan, B.; DePaula-Silva, A.B.; Rodesch, C.; Barker, E.; Bosque, A.; Planelles, V. Downmodulation of CCR7 by HIV-1 Vpu results in impaired migration and chemotactic signaling within CD4(+) T cells. Cell Rep. 2014, 7, 2019–2030.
166. Vassena, L.; Giuliani, E.; Koppensteiner, H.; Bolduan, S.; Schindler, M.; Doria, M. HIV-1 Nef and Vpu Interfere with L-Selectin (CD62L) Cell Surface Expression To Inhibit Adhesion and Signaling in Infected CD4+ T Lymphocytes. J. Virol. 2015, 89, 5687–5700.
167. Comerford, I.; Harata-Lee, Y.; Bunting, M.D.; Gregor, C.; Kara, E.E.; McColl, S.R. A myriad of functions and complex regulation of the CCR7/CCL19/CCL21 chemokine axis in the adaptive immune system. Cytokine Growth Factor Rev. 2013, 24, 269–283.
168. Khan, A.I.; Kubes, P. L-selectin: An emerging player in chemokine function. Microcirculation 2003, 10, 351–358.
169. Varoqui, H.; Zhu, H.; Yao, D.; Ming, H.; Erickson, J.D. Cloning and functional identification of a neuronal glutamine transporter. J. Biol. Chem. 2000, 275, 4049–4054.
170. Wang, R.; Dillon, C.P.; Shi, L.Z.; Milasta, S.; Carter, R.; Finkelstein, D.; McCormick, L.L.; Fitzgerald, P.; Chi, H.; Munger, J.; et al. The transcription factor Myc controls metabolic reprogramming upon T lymphocyte activation. Immunity 2011, 35, 871–882.
171. Sugden, S.; Cohen, E.A. Attacking the Supply Lines: HIV-1 Restricts Alanine Uptake to Prevent T Cell Activation. Cell Host Microbe 2015, 18, 514–517.
172. Tokarev, A.; Guatelli, J. Misdirection of membrane trafficking by HIV-1 Vpu and Nef: Keys to viral virulence and persistence. Cell. Logist. 2011, 1, 90–102.
173. Pawlak, E.N.; Dikeakos, J.D. HIV-1 Nef: a master manipulator of the membrane trafficking machinery mediating immune evasion. Biochim. Biophys. Acta 2015, 1850, 733–741.
174. Andrew, A.; Strebel, K. HIV-1 Vpu targets cell surface markers CD4 and BST-2 through distinct mechanisms. Mol. Asp. Med. 2010*, 31, 407–417.
175. Neil, S.J. The antiviral activities of tetherin. Curr. Top. Microbiol. Immunol. 2013, 371, 67–104.
176. Smithgall, T.E.; Thomas, G. Small molecule inhibitors of the HIV-1 virulence factor, Nef. Drug Discov. Today Technol. 2013, 10, e523–e529.
177. Mi, Z.; Ding, J.; Zhang, Q.; Zhao, J.; Ma, L.; Yu, H.; Liu, Z.; Shan, G.; Li, X.; Zhou, J.; et al. A small molecule compound IMB-LA inhibits HIV-1 infection by preventing viral Vpu from antagonizing the host restriction factor BST-2. Sci. Rep. 2015, 5, 18499.