Blocking premature reverse transcription fails to rescue the HIV-1 nucleocapsid-mutant replication defect

Retrovirology

Volumn 8, Issue , 2011, Pages

  Thomas, James A ^a   Shatzer, Teresa L ^a   Gorelick, Robert J ^a  

^a SAIC FREDERICK INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CD4 ANTIGEN; NEVIRAPINE; TENOFOVIR; GAG PROTEIN; MUTANT PROTEIN; NC71 PROTEIN, HUMAN IMMUNODEFICIENCY VIRUS 1;

ANTIVIRAL ACTIVITY; ARTICLE; CELL CULTURE; CONTROLLED STUDY; HUMAN IMMUNODEFICIENCY VIRUS 1; IC 50; NONHUMAN; NUCLEOTIDE SEQUENCE; PLASMID; PROVIRUS; REVERSE TRANSCRIPTION; VIRUS INFECTIVITY; VIRUS MUTANT; VIRUS NUCLEOCAPSID; VIRUS REPLICATION; VIRUS TITRATION; WILD TYPE; CELL LINE; GENETICS; GROWTH, DEVELOPMENT AND AGING; HUMAN; METABOLISM; MISSENSE MUTATION; VIRUS DNA CELL DNA INTERACTION;

HUMAN IMMUNODEFICIENCY VIRUS 1;

CELL LINE; GAG GENE PRODUCTS, HUMAN IMMUNODEFICIENCY VIRUS; HIV-1; HUMANS; MUTANT PROTEINS; MUTATION, MISSENSE; REVERSE TRANSCRIPTION; VIRUS INTEGRATION; VIRUS REPLICATION;

EID: 79958846530     PISSN: None     EISSN: 17424690     Source Type: Journal    
DOI: 10.1186/1742-4690-8-46     Document Type: Article

References (78)

1. Levin JG, Guo J, Rouzina I, Musier-Forsyth K. Nucleic acid chaperone activity of HIV-1 nucleocapsid protein: Critical role in reverse transcription and molecular mechanism. Prog Nucleic Acid Res Mol Biol 2005, 80:217-286.
2. Rein A, Henderson LE, Levin JG. Nucleic-acid-chaperone activity of retroviral nucleocapsid proteins: significance for viral replication. Trends Biochem Sci 1998, 23:297-301. 10.1016/S0968-0004(98)01256-0, 9757830.
3. Thomas JA, Gorelick RJ. Nucleocapsid protein function in early infection processes. Virus Res 2008, 134:39-63. 10.1016/j.virusres.2007.12.006, 2789563, 18279991.
4. Bampi C, Jacquenet S, Lener D, Decimo D, Darlix JL. The chaperoning and assistance roles of the HIV-1 nucleocapsid protein in proviral DNA synthesis and maintenance. Int J Biochem Cell Biol 2004, 36:1668-1686. 10.1016/j.biocel.2004.02.024, 15183337.
5. Bampi C, Jacquenet S, Lener D, Decimo D, Darlix JL. The chaperoning and assistance roles of the HIV-1 nucleocapsid protein in proviral DNA synthesis and maintenance. Curr HIV Res 2004, 2:79-92. 10.2174/1570162043485022, 15053342.
6. Levin JG, Mitra M, Mascarenhas A, Musier-Forsyth K. Role of HIV-1 nucleocapsid protein in HIV-1 reverse transcription. RNA Biol 2010, 7:754-774. 10.4161/rna.7.6.14115, 3073334, 21160280.
7. Godet J, Mely Y. Biophysical studies of the nucleic acid chaperone properties of the HIV-1 nucleocapsid protein. RNA Biol 2010, 7:48-60.
8. Mirambeau G, Lyonnais S, Gorelick RJ. Features, processing states, and heterologous protein interactions in the modulation of the retroviral nucleocapsid protein function. RNA Biol 2010, 7:85-95.
9. Khan R, Giedroc DP. Recombinant human immunodeficiency virus type 1 nucleocapsid (NCp7) protein unwinds tRNA. J Biol Chem 1992, 267:6689-6695.
10. Hargittai MR, Mangla AT, Gorelick RJ, Musier-Forsyth K. HIV-1 nucleocapsid protein zinc finger structures induce tRNA(Lys,3) structural changes but are not critical for primer/template annealing. J Mol Biol 2001, 312:985-997. 10.1006/jmbi.2001.5021, 11580244.
11. Guo F, Saadatmand J, Niu M, Kleiman L. Roles of Gag and NCp7 in facilitating tRNA(Lys)(3) Annealing to viral RNA in human immunodeficiency virus type 1. J Virol 2009, 83:8099-8107. 10.1128/JVI.00488-09, 2715748, 19494012.
12. Johnson PE, Turner RB, Wu ZR, Hairston L, Guo J, Levin JG, Summers MF. A mechanism for plus-strand transfer enhancement by the HIV-1 nucleocapsid protein during reverse transcription. Biochemistry 2000, 39:9084-9091. 10.1021/bi000841i, 10924101.
13. Guo J, Henderson LE, Bess J, Kane B, Levin JG. Human immunodeficiency virus type 1 nucleocapsid protein promotes efficient strand transfer and specific viral DNA synthesis by inhibiting TAR-dependent self-priming from minus-strand strong-stop DNA. J Virol 1997, 71:5178-5188. 191753, 9188585.
14. Guo J, Wu T, Anderson J, Kane BF, Johnson DG, Gorelick RJ, Henderson LE, Levin JG. Zinc finger structures in the human immunodeficiency virus type 1 nucleocapsid protein facilitate efficient minus- and plus-strand transfer. J Virol 2000, 74:8980-8988. 10.1128/JVI.74.19.8980-8988.2000, 102094, 10982342.
15. Guo J, Wu T, Kane BF, Johnson DG, Henderson LE, Gorelick RJ, Levin JG. Subtle alterations of the native zinc finger structures have dramatic effects on the nucleic acid chaperone activity of human immunodeficiency virus type 1 nucleocapsid protein. J Virol 2002, 76:4370-4378. 10.1128/JVI.76.9.4370-4378.2002, 155087, 11932404.
16. Rodriguez-Rodriguez L, Tsuchihashi Z, Fuentes GM, Bambara RA, Fay PJ. Influence of human immunodeficiency virus nucleocapsid protein on synthesis and strand transfer by the reverse transcriptase in vitro. J Biol Chem 1995, 270:15005-15011. 10.1074/jbc.270.25.15005, 7541033.
17. You JC, McHenry CS. Human immunodeficiency virus nucleocapsid protein accelerates strand transfer of the terminally redundant sequences involved in reverse transcription. J Biol Chem 1994, 269:31491-31495.
18. Heilman-Miller SL, Wu T, Levin JG. Alteration of nucleic acid structure and stability modulates the efficiency of minus-strand transfer mediated by the HIV-1 nucleocapsid protein. J Biol Chem 2004, 279:44154-44165. 10.1074/jbc.M401646200, 15271979.
19. Wu T, Heilman-Miller SL, Levin JG. Effects of nucleic acid local structure and magnesium ions on minus-strand transfer mediated by the nucleic acid chaperone activity of HIV-1 nucleocapsid protein. Nucleic Acids Res 2007, 35:3974-3987. 10.1093/nar/gkm375, 1919501, 17553835.
20. Hong MK, Harbron EJ, O'Connor DB, Guo J, Barbara PF, Levin JG, Musier-Forsyth K. Nucleic acid conformational changes essential for HIV-1 nucleocapsid protein-mediated inhibition of self-priming in minus-strand transfer. J Mol Biol 2003, 325:1-10. 10.1016/S0022-2836(02)01177-4, 12473448.
21. Golinelli MP, Hughes SH. Self-priming of retroviral minus-strand strong-stop DNAs. Virology 2001, 285:278-290. 10.1006/viro.2001.0970, 11437662.
22. Drummond JE, Mounts P, Gorelick RJ, Casas-Finet JR, Bosche WJ, Henderson LE, Waters DJ, Arthur LO. Wild-type and mutant HIV type 1 nucleocapsid proteins increase the proportion of long cDNA transcripts by viral reverse transcriptase. AIDS Res Hum Retroviruses 1997, 13:533-543. 10.1089/aid.1997.13.533, 9135871.
23. Ji X, Klarmann GJ, Preston BD. Effect of human immunodeficiency virus type 1 (HIV-1) nucleocapsid protein on HIV-1 reverse transcriptase activity in vitro. Biochemistry 1996, 35:132-143. 10.1021/bi951707e, 8555166.
24. Klasens BI, Huthoff HT, Das AT, Jeeninga RE, Berkhout B. The effect of template RNA structure on elongation by HIV-1 reverse transcriptase. Biochim Biophys Acta 1999, 1444:355-370.
25. Wu W, Henderson LE, Copeland TD, Gorelick RJ, Bosche WJ, Rein A, Levin JG. Human immunodeficiency virus type 1 nucleocapsid protein reduces reverse transcriptase pausing at a secondary structure near the murine leukemia virus polypurine tract. J Virol 1996, 70:7132-7142. 190766, 8794360.
26. Carteau S, Gorelick RJ, Bushman FD. Coupled integration of human immunodeficiency virus type 1 cDNA ends by purified integrase in vitro: stimulation by the viral nucleocapsid protein. J Virol 1999, 73:6670-6679. 112751, 10400764.
27. Tsuchihashi Z, Brown PO. DNA strand exchange and selective DNA annealing promoted by the human immunodeficiency virus type 1 nucleocapsid protein. J Virol 1994, 68:5863-5870. 236991, 8057466.
28. Gorelick RJ, Gagliardi TD, Bosche WJ, Wiltrout TA, Coren LV, Chabot DJ, Lifson JD, Henderson LE, Arthur LO. Strict conservation of the retroviral nucleocapsid protein zinc finger is strongly influenced by its role in viral infection processes: characterization of HIV-1 particles containing mutant nucleocapsid zinc-coordinating sequences. Virology 1999, 256:92-104. 10.1006/viro.1999.9629, 10087230.
29. Demene H, Dong CZ, Ottmann M, Rouyez MC, Jullian N, Morellet N, Mely Y, Darlix JL, Fournie-Zaluski MC, Saragosti S, et al. 1H NMR structure and biological studies of the His23--*Cys mutant nucleocapsid protein of HIV-1 indicate that the conformation of the first zinc finger is critical for virus infectivity. Biochemistry 1994, 33:11707-11716. 10.1021/bi00205a006, 7918387.
30. Julian N, Demene H, Morellet N, Maigret B, Roques BP. Replacement of His23 by Cys in a zinc finger of HIV-1 NCp7 led to a change in 1H NMR-derived 3D structure and to a loss of biological activity. FEBS Lett 1993, 331:43-48. 10.1016/0014-5793(93)80294-5, 8405409.
31. Buckman JS, Bosche WJ, Gorelick RJ. Human immunodeficiency virus type 1 nucleocapsid Zn(2+) fingers are required for efficient reverse transcription, initial integration processes, and protection of newly synthesized viral DNA. J Virol 2003, 77:1469-1480. 10.1128/JVI.77.2.1469-1480.2003, 140799, 12502862.
32. Thomas JA, Gagliardi TD, Alvord WG, Lubomirski M, Bosche WJ, Gorelick RJ. Human immunodeficiency virus type 1 nucleocapsid zinc-finger mutations cause defects in reverse transcription and integration. Virology 2006, 353:41-51. 10.1016/j.virol.2006.05.014, 16784767.
33. Thomas JA, Bosche WJ, Shatzer TL, Johnson DG, Gorelick RJ. Mutations in human immunodeficiency virus type 1 nucleocapsid protein zinc fingers cause premature reverse transcription. J Virol 2008, 82:9318-9328. 10.1128/JVI.00583-08, 2546943, 18667500.
34. Didierlaurent L, Houzet L, Morichaud Z, Darlix JL, Mougel M. The conserved N-terminal basic residues and zinc-finger motifs of HIV-1 nucleocapsid restrict the viral cDNA synthesis during virus formation and maturation. Nucleic Acids Res 2008, 36:4745-4753. 10.1093/nar/gkn474, 2504319, 18641038.
35. Houzet L, Morichaud Z, Didierlaurent L, Muriaux D, Darlix JL, Mougel M. Nucleocapsid mutations turn HIV-1 into a DNA-containing virus. Nucleic Acids Res 2008, 36:2311-2319. 10.1093/nar/gkn069, 2367716, 18296486.
36. Mougel M, Houzet L, Darlix JL. When is it time for reverse transcription to start and go?. Retrovirology 2009, 6:24. 10.1186/1742-4690-6-24, 2656454, 19261185.
37. Borroto-Esoda K, Boone LR. Development of a human immunodeficiency virus-1 in vitro DNA synthesis system to study reverse transcriptase inhibitors. Antiviral Res 1994, 23:235-249. 10.1016/0166-3542(94)90021-3, 7519003.
38. Balzarini J, Holy A, Jindrich J, Naesens L, Snoeck R, Schols D, De Clercq E. Differential antiherpesvirus and antiretrovirus effects of the (S) and (R) enantiomers of acyclic nucleoside phosphonates: potent and selective in vitro and in vivo antiretrovirus activities of (R)-9-(2-phosphonomethoxypropyl)-2,6-diaminopurine. Antimicrob Agents Chemother 1993, 37:332-338. 187663, 8452366.
39. Merluzzi VJ, Hargrave KD, Labadia M, Grozinger K, Skoog M, Wu JC, Shih CK, Eckner K, Hattox S, Adams J, et al. Inhibition of HIV-1 replication by a nonnucleoside reverse transcriptase inhibitor. Science 1990, 250:1411-1413. 10.1126/science.1701568, 1701568.
40. Ott DE, Coren LV, Johnson DG, Sowder RC, Arthur LO, Henderson LE. Analysis and localization of cyclophilin A found in the virions of human immunodeficiency virus type 1 MN strain. AIDS Res Hum Retroviruses 1995, 11:1003-1006. 10.1089/aid.1995.11.1003, 8554896.
41. Morcock DR, Thomas JA, Sowder RC, Henderson LE, Crise BJ, Gorelick RJ. HIV-1 inactivation by 4-vinylpyridine is enhanced by dissociating Zn(2+) from nucleocapsid protein. Virology 2008, 375:148-158. 10.1016/j.virol.2008.01.045, 2553892, 18304600.
42. Bampi C, Bibillo A, Wendeler M, Divita G, Gorelick RJ, Le Grice SF, Darlix JL. Nucleotide excision repair and template-independent addition by HIV-1 reverse transcriptase in the presence of nucleocapsid protein. J Biol Chem 2006, 281:11736-11743. 10.1074/jbc.M600290200, 16500895.
43. Boyer PL, Imamichi T, Sarafianos SG, Arnold E, Hughes SH. Effects of the Delta67 complex of mutations in human immunodeficiency virus type 1 reverse transcriptase on nucleoside analog excision. J Virol 2004, 78:9987-9997. 10.1128/JVI.78.18.9987-9997.2004, 515022, 15331732.
44. Grohmann D, Godet J, Mely Y, Darlix JL, Restle T. HIV-1 nucleocapsid traps reverse transcriptase on nucleic acid substrates. Biochemistry 2008, 47:12230-12240. 10.1021/bi801386r, 18947237.
45. Abram ME, Ferris AL, Shao W, Alvord WG, Hughes SH. Nature, position, and frequency of mutations made in a single cycle of HIV-1 replication. J Virol 2010, 84:9864-9878. 10.1128/JVI.00915-10, 2937799, 20660205.
46. Thomas JA, Shulenin S, Coren LV, Bosche WJ, Gagliardi TD, Gorelick RJ, Oroszlan S. Characterization of human immunodeficiency virus type 1 (HIV-1) containing mutations in the nucleocapsid protein at a putative HIV-1 protease cleavage site. Virology 2006, 354:261-270. 10.1016/j.virol.2006.07.011, 16904152.
47. Willey RL, Maldarelli F, Martin MA, Strebel K. Human immunodeficiency virus type 1 Vpu protein induces rapid degradation of CD4. J Virol 1992, 66:7193-7200. 240416, 1433512.
48. Chen BK, Gandhi RT, Baltimore D. CD4 down-modulation during infection of human T cells with human immunodeficiency virus type 1 involves independent activities of vpu, env, and nef. J Virol 1996, 70:6044-6053. 190625, 8709227.
49. Tanchou V, Decimo D, Pechoux C, Lener D, Rogemond V, Berthoux L, Ottmann M, Darlix JL. Role of the N-terminal zinc finger of human immunodeficiency virus type 1 nucleocapsid protein in virus structure and replication. J Virol 1998, 72:4442-4447. 109678, 9557738.
50. Lyonnais S, Gorelick RJ, Mergny JL, Le Cam E, Mirambeau G. G-quartets direct assembly of HIV-1 nucleocapsid protein along single-stranded DNA. Nucleic Acids Res 2003, 31:5754-5763. 10.1093/nar/gkg716, 206446, 14500839.
51. Mirambeau G, Lyonnais S, Coulaud D, Hameau L, Lafosse S, Jeusset J, Justome A, Delain E, Gorelick RJ, Le Cam E. Transmission electron microscopy reveals an optimal HIV-1 nucleocapsid aggregation with single-stranded nucleic acids and the mature HIV-1 nucleocapsid protein. J Mol Biol 2006, 364:496-511. 10.1016/j.jmb.2006.08.065, 17020765.
52. Mirambeau G, Lyonnais S, Coulaud D, Hameau L, Lafosse S, Jeusset J, Borde I, Reboud-Ravaux M, Restle T, Gorelick RJ, Le Cam E. HIV-1 protease and reverse transcriptase control the architecture of their nuclecapsid partner. PLoS One 2007, 2:e669. 10.1371/journal.pone.0000669, 1940317, 17712401.
53. Cruceanu M, Urbaneja MA, Hixson CV, Johnson DG, Datta SA, Fivash MJ, Stephen AG, Fisher RJ, Gorelick RJ, Casas-Finet JR, et al. Nucleic acid binding and chaperone properties of HIV-1 Gag and nucleocapsid proteins. Nucleic Acids Res 2006, 34:593-605. 10.1093/nar/gkj458, 1356529, 16449201.
54. Zhang H, Dornadula G, Orenstein J, Pomerantz RJ. Morphologic changes in human immunodeficiency virus type 1 virions secondary to intravirion reverse transcription: evidence indicating that reverse transcription may not take place within the intact viral core. J Hum Virol 2000, 3:165-172.
55. Stremlau M, Perron M, Lee M, Li Y, Song B, Javanbakht H, Diaz-Griffero F, Anderson DJ, Sundquist WI, Sodroski J. Specific recognition and accelerated uncoating of retroviral capsids by the TRIM5alpha restriction factor. Proc Natl Acad Sci USA 2006, 103:5514-5519. 10.1073/pnas.0509996103, 1459386, 16540544.
56. Nisole S, Saib A. Early steps of retrovirus replicative cycle. Retrovirology 2004, 1:9. 10.1186/1742-4690-1-9, 421752, 15169567.
57. Warrilow D, Tachedjian G, Harrich D. Maturation of the HIV reverse transcription complex: putting the jigsaw together. Rev Med Virol 2009, 19:324-337. 10.1002/rmv.627, 19750561.
58. Dismuke DJ, Aiken C. Evidence for a functional link between uncoating of the human immunodeficiency virus type 1 core and nuclear import of the viral preintegration complex. J Virol 2006, 80:3712-3720. 10.1128/JVI.80.8.3712-3720.2006, 1440469, 16571788.
59. Auewarakul P, Wacharapornin P, Srichatrapimuk S, Chutipongtanate S, Puthavathana P. Uncoating of HIV-1 requires cellular activation. Virology 2005, 337:93-101. 10.1016/j.virol.2005.02.028, 15882886.
60. Iordanskiy S, Berro R, Altieri M, Kashanchi F, Bukrinsky M. Intracytoplasmic maturation of the human immunodeficiency virus type 1 reverse transcription complexes determines their capacity to integrate into chromatin. Retrovirology 2006, 3:4. 10.1186/1742-4690-3-4, 1360674, 16409631.
61. Arhel N. Revisiting HIV-1 uncoating. Retrovirology 2010, 7:96. 10.1186/1742-4690-7-96, 2998454, 21083892.
62. Williams MC, Gorelick RJ, Musier-Forsyth K. Specific zinc-finger architecture required for HIV-1 nucleocapsid protein's nucleic acid chaperone function. Proc Natl Acad Sci USA 2002, 99:8614-8619. 10.1073/pnas.132128999, 124332, 12084921.
63. de Marco A, Muller B, Glass B, Riches JD, Krausslich HG, Briggs JA. Structural Analysis of HIV-1 Maturation Using Cryo-Electron Tomography. PLoS Pathog 2010, 6:e1001215. 10.1371/journal.ppat.1001215, 2999899, 21151640.
64. Chertova E, Bess JW, Crise BJ, Sowder IR, Schaden TM, Hilburn JM, Hoxie JA, Benveniste RE, Lifson JD, Henderson LE, Arthur LO. Envelope glycoprotein incorporation, not shedding of surface envelope glycoprotein (gp120/SU), Is the primary determinant of SU content of purified human immunodeficiency virus type 1 and simian immunodeficiency virus. J Virol 2002, 76:5315-5325. 10.1128/JVI.76.11.5315-5325.2002, 137021, 11991960.
65. Warrilow D, Stenzel D, Harrich D. Isolated HIV-1 core is active for reverse transcription. Retrovirology 2007, 4:77. 10.1186/1742-4690-4-77, 2169257, 17956635.
66. Adachi A, Gendelman HE, Koenig S, Folks T, Willey R, Rabson A, Martin MA. Production of acquired immunodeficiency syndrome-associated retrovirus in human and nonhuman cells transfected with an infectious molecular clone. J Virol 1986, 59:284-291. 253077, 3016298.
67. Ott DE, Chertova EN, Busch LK, Coren LV, Gagliardi TD, Johnson DG. Mutational analysis of the hydrophobic tail of the human immunodeficiency virus type 1 p6(Gag) protein produces a mutant that fails to package its envelope protein. J Virol 1999, 73:19-28. 103803, 9847302.
68. Burns JC, Friedmann T, Driever W, Burrascano M, Yee JK. Vesicular stomatitis virus G glycoprotein pseudotyped retroviral vectors: concentration to very high titer and efficient gene transfer into mammalian and nonmammalian cells. Proc Natl Acad Sci USA 1993, 90:8033-8037. 10.1073/pnas.90.17.8033, 47282, 8396259.
69. DuBridge RB, Tang P, Hsia HC, Leong PM, Miller JH, Calos MP. Analysis of mutation in human cells by using an Epstein-Barr virus shuttle system. Mol Cell Biol 1987, 7:379-387. 365079, 3031469.
70. Pear WS, Nolan GP, Scott ML, Baltimore D. Production of high-titer helper-free retroviruses by transient transfection. Proc Natl Acad Sci USA 1993, 90:8392-8396. 10.1073/pnas.90.18.8392, 47362, 7690960.
71. Chesebro B, Buller R, Portis J, Wehrly K. Failure of human immunodeficiency virus entry and infection in CD4-positive human brain and skin cells. J Virol 1990, 64:215-221. 249089, 2293663.
72. Chesebro B, Wehrly K. Development of a sensitive quantitative focal assay for human immunodeficiency virus infectivity. J Virol 1988, 62:3779-3788. 253522, 3047430.
73. Chesebro B, Wehrly K, Metcalf J, Griffin DE. Use of a new CD4-positive HeLa cell clone for direct quantitation of infectious human immunodeficiency virus from blood cells of AIDS patients. J Infect Dis 1991, 163:64-70. 10.1093/infdis/163.1.64, 1984477.
74. Platt EJ, Bilska M, Kozak SL, Kabat D, Montefiori DC. Evidence that ecotropic murine leukemia virus contamination in TZM-bl cells does not affect the outcome of neutralizing antibody assays with human immunodeficiency virus type 1. J Virol 2009, 83:8289-8292. 10.1128/JVI.00709-09, 2715758, 19474095.
75. Takeuchi Y, McClure MO, Pizzato M. Identification of gammaretroviruses constitutively released from cell lines used for human immunodeficiency virus research. J Virol 2008, 82:12585-12588. 10.1128/JVI.01726-08, 2593302, 18842727.
76. Wei X, Decker JM, Liu H, Zhang Z, Arani RB, Kilby JM, Saag MS, Wu X, Shaw GM, Kappes JC. Emergence of resistant human immunodeficiency virus type 1 in patients receiving fusion inhibitor (T-20) monotherapy. Antimicrob Agents Chemother 2002, 46:1896-1905. 10.1128/AAC.46.6.1896-1905.2002, 127242, 12019106.
77. Derdeyn CA, Decker JM, Sfakianos JN, Wu X, O'Brien WA, Ratner L, Kappes JC, Shaw GM, Hunter E. Sensitivity of human immunodeficiency virus type 1 to the fusion inhibitor T-20 is modulated by coreceptor specificity defined by the V3 loop of gp120. J Virol 2000, 74:8358-8367. 10.1128/JVI.74.18.8358-8367.2000, 116346, 10954535.
78. Platt EJ, Wehrly K, Kuhmann SE, Chesebro B, Kabat D. Effects of CCR5 and CD4 cell surface concentrations on infections by macrophagetropic isolates of human immunodeficiency virus type 1. J Virol 1998, 72:2855-2864. 109730, 9525605.