Distinct HIV-1 entry phenotypes are associated with transmission, subtype specificity, and resistance to broadly neutralizing antibodies

Retrovirology

Benhur Lee²  Paul R Gorry⁵  Jasminka Sterjovski³  Katharina Borm⁴  Tom Chou¹  Nicholas E Webb⁶  Kelechi Chikere⁶ 

[1] Department of Biomathematics, University of California at Los Angeles, Los Angeles, CA, USA;Department of Microbiology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, #1124, New York, NY 10029, USA;Department of Infectious Diseases, Monash University, Melbourne, VIC, Australia;Center for Biomedical Research, Burnet Institute, Melbourne, VIC, Australia;Department of Microbiology and Immunology, University of Melbourne, Melbourne, VIC, Australia;Department of Microbiology, Immunology, and Molecular Genetics, Los Angeles, USA

关键词: Receptor affinity profiling;    Broadly neutralizing antibodies;    Subtype C;    Acute transmitted/founder envelopes;    Receptor usage efficiency;    CCR5;    CD4;    Virus entry;   

Others  :  1131847
DOI  :  10.1186/1742-4690-11-48

 received in 2014-01-20, accepted in 2014-06-03,  发布年份 2014

【 摘 要 】

Background

The efficiency of CD4/CCR5 mediated HIV-1 entry has important implications for pathogenesis and transmission. The HIV-1 receptor affinity profiling (Affinofile) system analyzes and quantifies the infectivity of HIV-1 envelopes (Envs) across a spectrum of CD4/CCR5 expression levels and distills these data into a set of Affinofile metrics. The Affinofile system has shed light on how differential CD4/CCR5 usage efficiencies contributes to an array of Env phenotypes associated with cellular tropism, viral pathogenesis, and CCR5 inhibitor resistance. To facilitate more rapid, convenient, and robust analysis of HIV-1 entry phenotypes, we engineered a reporter Affinofile system containing a Tat- and Rev-dependent Gaussia luciferase-eGFP-Reporter (GGR) that is compatible with the use of pseudotyped or replication competent viruses with or without a virally encoded reporter gene. This GGR Affinofile system enabled a higher throughput characterization of CD4/CCR5 usage efficiencies associated with differential Env phenotypes.

Results

We first validated our GGR Affinofile system on isogenic JR-CSF Env mutants that differ in their affinity for CD4 and/or CCR5. We established that their GGR Affinofile metrics reflected their differential entry phenotypes on primary PBMCs and CD4+ T-cell subsets. We then applied GGR Affinofile profiling to reveal distinct entry phenotypes associated with transmission, subtype specificity, and resistance to broadly neutralizing antibodies (BNAbs). First, we profiled a panel of reference subtype B transmitted/founder (T/F) and chronic Envs (n = 12) by analyzing the infectivity of each Env across 25 distinct combinations of CD4/CCR5 expression levels. Affinofile metrics revealed that at low CCR5 levels, our panel of subtype B T/F Envs was more dependent on high levels of CD4 for HIV-1 entry compared to chronic Envs. Next, we analyzed a reference panel of 28 acute/early subtype A-D Envs, and noted that subtype C Envs could be distinguished from the other subtypes based on their infectivity profiles and relevant Affinofile metrics. Lastly, mutations known to confer resistance to VRC01 or PG6/PG19 BNAbs, when engineered into subtypes A-D Envs, resulted in significantly decreased CD4/CCR5 usage efficiency.

Conclusions

GGR Affinofile profiling reveals pathophysiological phenotypes associated with varying HIV-1 entry efficiencies, and highlight the fitness costs associated with resistance to some broadly neutralizing antibodies.

【 授权许可】

   
2014 Chikere et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Wilen CB, Tilton JC, Doms RW: Molecular mechanisms of HIV entry. Adv Exp Med Biol 2012, 726:223-242.
• [2]Connor RI, Sheridan KE, Ceradini D, Choe S, Landau NR: Change in coreceptor use correlates with disease progression in HIV-1–infected individuals. J Exp Med 1997, 185:621-628.
• [3]Bjorndal A, Deng H, Jansson M, Fiore JR, Colognesi C, Karlsson A, Albert J, Scarlatti G, Littman DR, Fenyo EM: Coreceptor usage of primary human immunodeficiency virus type 1 isolates varies according to biological phenotype. J Virol 1997, 71:7478-7487.
• [4]Spira S, Wainberg M, Loemba H, Turner D, Brenner B: Impact of clade diversity on HIV-1 virulence, antiretroviral drug sensitivity and drug resistance. J Antimicrob Chemoth 2003, 51:229-240.
• [5]Gorry PR, Ancuta P: Coreceptors and HIV-1 Pathogenesis. Curr HIV/AIDS Rep 2010, 8:45-53.
• [6]Jakobsen MR, Cashin K, Roche M, Sterjovski J, Ellett A, Borm K, Flynn J, Erikstrup C, Gouillou M, Gray LR, Saksena NK, Wang B, Purcell DF, Kallestrup P, Zinyama-Gutsire R, Gomo E, Ullum H, Ostergaard L, Lee B, Ramsland PA, Churchill MJ, Gorry PR: Longitudinal analysis of CCR5 and CXCR4 usage in a cohort of antiretroviral therapy-naive subjects with progressive HIV-1 subtype C infection. PLoS One 2013, 8:e65950.
• [7]Trkola A, Dragic T, Arthos J, Binley JM, Olson WC, Allaway GP, Cheng-Mayer C, Robinson J, Maddon PJ, Moore JP: CD4-dependent, antibody-sensitive interactions between HIV-1 and its co-receptor CCR-5. Nature 1996, 384:184-187.
• [8]Blaak H, Ran LJ, Rientsma R, Schuitemaker H: Susceptibility of in vitro stimulated PBMC to infection with NSI HIV-1 is associated with levels of CCR5 expression and beta-chemokine production. Virology 2000, 267:237-246.
• [9]Li S, Juarez J, Alali M, Dwyer D, Collman R, Cunningham A, Naif HM: Persistent CCR5 utilization and enhanced macrophage tropism by primary blood human immunodeficiency virus type 1 isolates from advanced stages of disease and comparison to tissue-derived isolates. J Virol 1999, 73:9741-9755.
• [10]Tuttle DL, Anders CB, Aquino-De Jesus MJ, Poole PP, Lamers SL, Briggs DR, Pomeroy SM, Alexander L, Peden KW, Andiman WA, Sleasman JW, Goodenow MM: Increased replication of non-syncytium-inducing HIV type 1 isolates in monocyte-derived macrophages is linked to advanced disease in infected children. AIDS Res Hum Retrov 2002, 18:353-362.
• [11]Smit TK, Wang B, Ng T, Osborne R, Brew B, Saksena NK: Varied tropism of HIV-1 isolates derived from different regions of adult brain cortex discriminate between patients with and without AIDS dementia complex (ADC): evidence for neurotropic HIV variants. Virology 2001, 279:509-526.
• [12]Gray L, Sterjovski J, Churchill M, Ellery P, Nasr N, Lewin SR, Crowe SM, Wesselingh SL, Cunningham AL, Gorry PR: Uncoupling coreceptor usage of human immunodeficiency virus type 1 (HIV-1) from macrophage tropism reveals biological properties of CCR5-restricted HIV-1 isolates from patients with acquired immunodeficiency syndrome. Virology 2005, 337:384-398.
• [13]Gorry PR, Francella N, Lewin SR, Collman RG: HIV-1 envelope-receptor interactions required for macrophage infection and implications for current HIV-1 cure strategies. J Leukoc Biol 2014, 95:71-81.
• [14]Sterjovski J, Churchill MJ, Ellett A, Gray LR, Roche MJ, Dunfee RL, Purcell DFJ, Saksena N, Wang B, Sonza S, Wang B, Sonza S, Wesselingh SL, Karlsson I, Fenyo EM, Gabuzda D, Cunningham AL, Gorry PR: Asn 362 in gp120 contributes to enhanced fusogenicity by CCR5-restricted HIV-1 envelope glycoprotein variants from patients with AIDS. Retrovirology 2007, 4:89.
• [15]Wade J, Sterjovski J, Gray L, Roche M, Chiavaroli L, Ellett A, Jakobsen MR, Cowley D, da Fonseca Pereira C, Saksena N, Wang B, Purcell DF, Karlsson I, Fenyö EM, Churchill M, Gorry PR: Enhanced CD4+ cellular apoptosis by CCR5-restricted HIV-1 envelope glycoprotein variants from patients with progressive HIV-1 infection. Virology 2010, 396:246-255.
• [16]Chang J, Jozwiak R, Wang B, Ng T, Ge YC, Bolton W, Dwyer DE, Randle C, Osborn R, Cunningham AL, Saksena NK: Unique HIV type 1 V3 region sequences derived from six different regions of brain: region-specific evolution within host-determined quasispecies. AIDS Res Hum Retrov 1998, 14:25-30.
• [17]Choe H, Farzan M, Sun Y, Sullivan N, Rollins B, Ponath PD, Wu L, Mackay CR, LaRosa G, Newman W, Gerard N, Gerard C, Sodroski J: The beta-chemokine receptors CCR3 and CCR5 facilitate infection by primary HIV-1 isolates. Cell 1996, 85:1135-1148.
• [18]Hill CM, Kwon D, Jones M, Davis CB, Marmon S, Daugherty BL, DeMartino JA, Springer MS, Unutmaz D, Littman DR: The amino terminus of human CCR5 is required for its function as a receptor for diverse human and simian immunodeficiency virus envelope glycoproteins. Virology 1998, 248:357-371.
• [19]Hoffman TL, Doms RW: HIV-1 envelope determinants for cell tropism and chemokine receptor use. Mol Membr Biol 1999, 16:57-65.
• [20]Lee B, Sharron M, Montaner LJ, Weissman D, Doms RW: 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 1999, 96:5215-5220.
• [21]Korber BT, Kunstman KJ, Patterson BK, Furtado M, McEvilly MM, Levy R, Wolinsky SM: Genetic differences between blood- and brain-derived viral sequences from human immunodeficiency virus type 1-infected patients: evidence of conserved elements in the V3 region of the envelope protein of brain-derived sequences. J Virol 1994, 68:7467-7481.
• [22]Martín-García J, Cao W, Varela-Rohena A, Plassmeyer ML, González-Scarano F: HIV-1 tropism for the central nervous system: brain-derived envelope glycoproteins with lower CD4 dependence and reduced sensitivity to a fusion inhibitor. Virology 2006, 346:169-179.
• [23]Ogert RA, Ba L, Hou Y, Buontempo C, Qiu P, Duca J, Murgolo N, Buontempo P, Ralston R, Howe JA: Structure-function analysis of human immunodeficiency virus type 1 gp120 amino acid mutations associated with resistance to the CCR5 coreceptor antagonist vicriviroc. J Virol 2009, 83:12151-12163.
• [24]Peters P, Dueñas-Decamp MJ, Sullivan WM, Clapham PR: Variation of macrophage tropism among HIV-1 R5 envelopes in brain and other tissues. J NeuroImmune Pharm 2007, 2:32-41.
• [25]Dejucq N, Simmons G, Clapham PR: Expanded tropism of primary human immunodeficiency virus type 1 R5 strains to CD4(+) T-cell lines determined by the capacity to exploit low concentrations of CCR5. J Virol 1999, 73:7842-7847.
• [26]Pakarasang M, Wasi C, Suwanagool S, Chalermchockcharoenkit A, Auewarakul P: Increased HIV-DNA load in CCR5-negative lymphocytes without viral phenotypic change. Virology 2006, 347:372-378.
• [27]Pugach P, Ray N, Klasse PJ, Ketas TJ, Michael E, Doms RW, Lee B, Moore JP: Inefficient entry of vicriviroc-resistant HIV-1 via the inhibitor-CCR5 complex at low cell surface CCR5 densities. Virology 2009, 387:296-302.
• [28]Roche M, Jakobsen MR, Sterjovski J, Ellett A, Posta F, Lee B, Jubb B, Westby M, Lewin SR, Ramsland PA, Churchill MJ, Gorry PR: HIV-1 escape from the CCR5 antagonist maraviroc associated with an altered and less-efficient mechanism of gp120-CCR5 engagement that attenuates macrophage tropism. J Virol 2011, 85:4330-4342.
• [29]Roche M, Salimi H, Duncan R, Wilkinson BL, Chikere K, Moore MS, Webb NE, Zappi H, Sterjovski J, Flynn JK, Lewin SR, Payne RJ, Churchill MJ, Gorry PR: A common mechanism of clinical HIV-1 resistance to the CCR5 antagonist maraviroc despite divergent resistance levels and lack of common gp120 resistance mutations. Retrovirology 2013, 10:43.
• [30]Salazar-Gonzalez JF, Salazar MG, Keele BF, Learn GH, Giorgi EE, Li H, Decker JM, Wang S, Baalwa J, Kraus MH, Parrish NF, Shaw KS, Guffey MB, Bar KJ, Davis KL, Ochsenbauer-Jambor C, Kappes JC, Saag MS, Cohen MS, Mulenga J, Derdeyn CA, Allen S, Hunter E, Markowitz M, Hraber P, Perelson AS, Bhattacharya T, Haynes BF, Korber BT, Hahn BH, 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.
• [31]Arrildt KT, Joseph SB, Swanstrom R: The HIV-1 env protein: a coat of many colors. Curr HIV/AIDS Rep 2012, 9:52-63.
• [32]Mosier DE: How HIV changes its tropism: evolution and adaptation? Curr Opin HIV AIDS 2009, 4:125-130.
• [33]Duenas-Decamp MJ, Peters PJ, Repik A, Musich T, Gonzalez-Perez MP, Caron C, Brown R, Ball J, Clapham PR: Variation in the biological properties of HIV-1 R5 envelopes: implications of envelope structure, transmission and pathogenesis. Future Virol 2010, 5:435-451.
• [34]Johnston SH, Lobritz MA, Nguyen S, Lassen K, Delair S, Posta F, Bryson YJ, Arts EJ, Chou T, Lee B: A quantitative affinity-profiling system that reveals distinct CD4/CCR5 usage patterns among human immunodeficiency virus type 1 and simian immunodeficiency virus strains. J Virol 2009, 83:11016-11026.
• [35]Roche M, Jakobsen MR, Ellett A, Salimiseyedabad H, Jubb B, Westby M, Lee B, Lewin SR, Churchill MJ, Gorry PR: HIV-1 predisposed to acquiring resistance to maraviroc (MVC) and other CCR5 antagonists in vitro has an inherent, low-level ability to utilize MVC-bound CCR5 for entry. Retrovirology 2011, 8:89.
• [36]Pfaff JM, Wilen CB, Harrison JE, Demarest JF, Lee B, Doms RW, Tilton JC: HIV-1 resistance to CCR5 antagonists associated with highly efficient use of CCR5 and altered tropism on primary CD4+ T cells. J Virol 2010, 84:6505-6514.
• [37]Agrawal-Gamse C, Lee FH, Haggarty B, Jordan APO, Yi Y, Lee B, Collman RG, Hoxie JA, Doms RW, Laakso MM: Adaptive mutations in a human immunodeficiency virus type 1 envelope protein with a truncated V3 loop restore function by improving interactions with CD4. J Virol 2009, 83:11005-11015.
• [38]Salimi H, Roche M, Webb N, Gray LR, Chikere K, Sterjovski J, Ellett A, Wesselingh SL, Ramsland PA, Lee B, Churchill MJ, Gorry PR: Macrophage-tropic HIV-1 variants from brain demonstrate alterations in the way gp120 engages both CD4 and CCR5. J Leukoc Biol 2013, 93:113-126.
• [39]Chikere K, Chou T, Gorry PR, Lee B: Affinofile profiling: how efficiency of CD4/CCR5 usage impacts the biological and pathogenic phenotype of HIV. Virology 2013, 435:81-91.
• [40]Wu Y, Beddall MH, Marsh JW: Rev-dependent lentiviral expression vector. Retrovirology 2007, 4:12.
• [41]Wu Y, Beddall MH, Marsh JW: Rev-dependent indicator T cell line. Curr HIV Res 2007, 5:394-402.
• [42]Boyd MT, Simpson GR, Cann AJ, Johnson MA, Weiss RA: A single amino acid substitution in the V1 loop of human immunodeficiency virus type 1 gp120 alters cellular tropism. J Virol 1993, 67:3649-3652.
• [43]Musich T, Peters PJ, Duenas-Decamp MJ, Gonzalez-Perez MP, Robinson J, Zolla-Pazner S, Ball JK, Luzuriaga K, Clapham PR: A conserved determinant in the V1 loop of HIV-1 modulates the V3 loop to prime Low CD4 Use and macrophage infection. J Virol 2011, 85:8.
• [44]Reeves JD: Sensitivity of HIV-1 to entry inhibitors correlates with envelope/coreceptor affinity, receptor density, and fusion kinetics. Proc Natl Acad Sci U S A 2002, 99:16249-16254.
• [45]Rizzuto CD: A conserved HIV gp120 glycoprotein structure involved in chemokine receptor binding. Science 1998, 280:1949-1953.
• [46]Oswald-Richter K, Grill SM, Leelawong M, Tseng M, Kalams SA, Hulgan T, Haas DW, Unutmaz D: Identification of a CCR5-expressing T cell subset that is resistant to R5-tropic HIV infection. PLoS Pathog 2007, 3:e58.
• [47]Virgin HW, Walker BD: Immunology and the elusive AIDS vaccine. Nature 2010, 464:224-231.
• [48]Haase AT: Targeting early infection to prevent HIV-1 mucosal transmission. Nature 2010, 464:217-223.
• [49]Grivel J-C, Shattock RJ, Margolis LB: Selective transmission of R5 HIV-1 variants: where is the gatekeeper? J Transl Med 2010, 9:S6.
• [50]Keele BF, Giorgi EE, Salazar-Gonzalez JF, Decker JM, Pham KT, Salazar MG, Sun C, Grayson T, Wang S, Li H, Wei X, Jiang C, Kirchherr JL, Gao F, Anderson JA, Ping LH, Swanstrom R, Tomaras GD, Blattner WA, Goepfert PA, Kilby JM, Saag MS, Delwart EL, Busch MP, Cohen MS, Montefiori DC, Haynes BF, Gaschen B, Athreya GS, Lee HY, et al: Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection. Proc Natl Acad Sci U S A 2008, 105:7552-7557.
• [51]Walker LM, Phogat SK, Chan-Hui PY, Wagner D, Phung P, Goss JL, Wrin T, Simek MD, Fling S, Mitcham JL, Lehrman JK, Priddy FH, Olsen OA, Frey SM, Hammond PW, Principal Investigators PG, Kaminsky S, Zamb T, Moyle M, Koff WC, Poignard P, Burton DR: Broad and potent neutralizing antibodies from an African donor reveal a new HIV-1 vaccine target. Science 2009, 326:285-289.
• [52]Zhou T, Georgiev I, Wu X, Yang Z-Y, Dai K, Finzi A, Kwon YD, Scheid JF, Shi W, Xu L, Yang Y, Zhu J, Nussenzweig MC, Sodroski J, Shapiro L, Nabel GJ, Mascola JR, Kwong PD: Structural basis for broad and potent neutralization of HIV-1 by antibody VRC01. Science 2010, 329:811-817.
• [53]Li Y, O’Dell S, Walker LM, Wu X, Guenaga J, Feng Y, Schmidt SD, McKee K, Louder MK, Ledgerwood JE, Graham BS, Haynes BF, Burton DR, Wyatt RT, Mascola JR: Mechanism of neutralization by the broadly neutralizing HIV-1 monoclonal antibody VRC01. J Virol 2011, 85:8954-8967.
• [54]Trkola A, Lassen KG, Lobritz MA, Bailey JR, Johnston S, Nguyen S, Lee B, Chou T, Siliciano RF, Markowitz M, Arts EJ: Elite suppressor–derived HIV-1 envelope glycoproteins exhibit reduced entry efficiency and kinetics. Plos Pathog 2009, 5:e1000377.
• [55]Tilton JC, Wilen CB, Didigu CA, Sinha R, Harrison JE, Agrawal-Gamse C, Henning EA, Bushman FD, Martin JN, Deeks SG, Doms RW: A maraviroc-resistant HIV-1 with narrow cross-resistance to other CCR5 antagonists depends on both N-terminal and extracellular loop domains of drug-bound CCR5. J Virol 2010, 84:10863-10876.
• [56]Jiang C, Parrish NF, Wilen CB, Li H, Chen Y, Pavlicek JW, Berg A, Lu X, Song H, Tilton JC, Pfaff JM, Henning EA, Decker JM, Moody MA, Drinker MS, Schutte R, Freel S, Tomaras GD, Nedellec R, Mosier DE, Haynes BF, Shaw GM, Hahn BH, Doms RW, Gao F: Primary infection by a human immunodeficiency virus with atypical coreceptor tropism. J Virol 2011, 85:10669-10681.
• [57]Bleul CC, Wu L, Hoxie JA, Springer TA, Mackay CR: The HIV coreceptors CXCR4 and CCR5 are differentially expressed and regulated on human T lymphocytes. Proc Natl Acad Sci U S A 1997, 94:1925-1930.
• [58]Mo H, Monard S, Pollack H, Ip J, Rochford G, Wu L, Hoxie J, Borkowsky W, Ho DD, Moore JP: Expression patterns of the HIV type 1 coreceptors CCR5 and CXCR4 on CD4+ T cells and monocytes from cord and adult blood. AIDS Res Hum Retrov 1998, 14:607-617.
• [59]Merk A, Subramaniam S: HIV-1 envelope glycoprotein structure. Curr Opin Structual Biol 2013, 23:8.
• [60]Benito JM, Zabay JM, Gil J, Bermejo M, Escudero A, Sanchez E, Fernandez-Cruz E: Quantitative alterations of the functionally distinct subsets of CD4 and CD8 T lymphocytes in asymptomatic HIV infection: changes in the expression of CD45RO, CD45RA, CD11b, CD38, HLA-DR, and CD25 antigens. J Acquir Immune Defic Syndr Hum Retrovirol 1997, 14:128-135.
• [61]Helbert MR, Walter J, L’Age J, Beverley PC: HIV infection of CD45RA + and CD45RO + CD4+ T cells. Clin Exp Immunol 1997, 107:300-305.
• [62]Spina CA, Prince HE, Richman DD: Preferential replication of HIV-1 in the CD45RO memory cell subset of primary CD4 lymphocytes in vitro. J Clin Invest 1997, 99:1774-1785.
• [63]Silvestri G, Zeng M, Southern PJ, Reilly CS, Beilman GJ, Chipman JG, Schacker TW, Haase AT: Lymphoid tissue damage in HIV-1 infection depletes naïve T cells and limits T cell reconstitution after antiretroviral therapy. Plos Pathog 2012, 8:e1002437.
• [64]Schacker TW, Brenchley JM, Beilman GJ, Reilly C, Pambuccian SE, Taylor J, Skarda D, Larson M, Douek DC, Haase AT: Lymphatic tissue fibrosis is associated with reduced numbers of naive CD4+ T cells in human immunodeficiency virus type 1 infection. Clin Vaccine Immunol 2006, 13:556-560.
• [65]Kwa D, Vingerhoed J, Boeser B, Schuitemaker H: Increased in vitro cytopathicity of CC chemokine receptor 5-restricted human immunodeficiency virus type 1 primary isolates correlates with a progressive clinical course of infection. J Infect Dis 2003, 187:1397-1403.
• [66]Duncan CJA, Sattentau QJ: Viral determinants of HIV-1 macrophage tropism. Viruses 2011, 3:2255-2279.
• [67]Cullen BR, Schnell G, Joseph S, Spudich S, Price RW, Swanstrom R: HIV-1 replication in the central nervous system occurs in Two distinct cell types. Plos Pathog 2011, 7:e1002286.
• [68]Salazar-Gonzalez JF, Bailes E, Pham KT, Salazar MG, Guffey MB, Keele BF, Derdeyn CA, Farmer P, Hunter E, Allen S, Derdeyn CA, Farmer P, Hunter E, Allen S, Manigart O, Mulenga J, Anderson JA, Swanstrom R, Haynes BF, Athreya GS, Korber BT, Sharp PM, Shaw GM, Hahn BH: Deciphering human immunodeficiency virus type 1 transmission and early envelope diversification by single-genome amplification and sequencing. J Virol 2008, 82:3952-3970.
• [69]Kearney M, Maldarelli F, Shao W, Margolick JB, Daar ES, Mellors JW, Rao V, Coffin JM, Palmer S: Human immunodeficiency virus type 1 population genetics and adaptation in newly infected individuals. J Virol 2008, 83:2715-2727.
• [70]Haaland RE, Hawkins PA, Salazar-Gonzalez J, Johnson A, Tichacek A, Karita E, Manigart O, Mulenga J, Keele BF, Shaw GM, Hahn BH, Allen SA, Derdeyn CA, Hunter E: Inflammatory genital infections mitigate a severe genetic bottleneck in heterosexual transmission of subtype a and C HIV-1. Plos Pathog 2009, 5:e1000274.
• [71]Masharsky Alexey E, Dukhovlinova Elena N, Verevochkin Sergei V, Toussova Olga V, Skochilov Roman V, Anderson Jeffrey A, Hoffman I, Cohen Myron S, Swanstrom R, Kozlov Andrei P: A substantial transmission bottleneck among newly and recently HIV‒1–infected injection drug users in St Petersburg. Russia J Infect Dis 2010, 201:1697-1702.
• [72]Gnanakaran S, Bhattacharya T, Daniels M, Keele BF, Hraber PT, Lapedes AS, Shen T, Gaschen B, Krishnamoorthy M, Li H, Decker JM, Salazar-Gonzalez JF, Wang S, Jiang C, Gao F, Swanstrom R, Anderson JA, Ping LH, Cohen MS, Markowitz M, Goepfert PA, Saag MS, Eron JJ, Hicks CB, Blattner WA, Tomaras GD, Asmal M, Letvin NL, Gilbert PB, Decamp AC, et al.: Recurrent signature patterns in HIV-1 B clade envelope glycoproteins associated with either early or chronic infections. Plos Pathog 2011, 7:e1002209.
• [73]Isaacman-Beck J, Hermann EA, Yi Y, Ratcliffe SJ, Mulenga J, Allen S, Hunter E, Derdeyn CA, Collman RG: Heterosexual transmission of human immunodeficiency virus type 1 subtype C: Macrophage tropism, alternative coreceptor use, and the molecular anatomy of CCR5 utilization. J Virol 2009, 83:8208-8220.
• [74]Alexander M, Lynch R, Mulenga J, Allen S, Derdeyn CA, Hunter E: Donor and recipient envs from heterosexual human immunodeficiency virus subtype C transmission pairs require high receptor levels for entry. J Virol 2010, 84:4100-4104.
• [75]Wilen CB, Parrish NF, Pfaff JM, Decker JM, Henning EA, Haim H, Petersen JE, Wojcechowskyj JA, Sodroski J, Haynes BF, Montefiori DC, Tilton JC, Shaw GM, Hahn BH, Doms RW: Phenotypic and immunologic comparison of clade B transmitted/founder and chronic HIV-1 envelope glycoproteins. J Virol 2011, 85:8514-8527.
• [76]Ochsenbauer C, Edmonds TG, Ding H, Keele BF, Decker J, Salazar MG, Salazar-Gonzalez JF, Shattock R, Haynes BF, Shaw GM, Hahn BH, Kappes JC: Generation of transmitted/founder HIV-1 infectious molecular clones and characterization of their replication capacity in CD4 T lymphocytes and monocyte-derived macrophages. J Virol 2011, 86:2715-2728.
• [77]Parrish NF, Wilen CB, Banks LB, Iyer SS, Pfaff JM, Salazar-Gonzalez JF, Salazar MG, Decker JM, Parrish EH, Berg A, Hopper J, Hora B, Kumar A, Mahlokozera T, Yuan S, Coleman C, Vermeulen M, Ding H, Ochsenbauer C, Tilton JC, Permar SR, Kappes JC, Betts MR, Busch MP, Gao F, Montefiori D, Haynes BF, Shaw GM, Hahn BH, Doms RW: Transmitted/founder and chronic subtype C HIV-1 Use CD4 and CCR5 receptors with equal efficiency and Are Not inhibited by blocking the integrin α4β7. Plos Pathog 2012, 8:e1002686.
• [78]Haim H, Si Z, Madani N, Wang L, Courter JR, Princiotto A, Kassa A, DeGrace M, McGee-Estrada K, Mefford M, Gabuzda D, Smith AB 3rd, Sodroski J: Soluble CD4 and CD4-mimetic compounds inhibit HIV-1 infection by induction of a short-lived activated state. Plos Pathog 2009, 5:e1000360.
• [79]Sterjovski J, Churchill MJ, Ellett A, Wesselingh SL, Ramsland PA, Gorry PR: Structural elements of primary CCR5-using HIV-1 gp120 proteins influencing sensitivity and resistance to the broadly neutralizing monoclonal antibody b12. Virology 2012, 432:394-404.
• [80]Parker ZF, Iyer SS, Wilen CB, Parrish NF, Chikere KC, Lee FH, Didigu CA, Berro R, Klasse PJ, Lee B, Moore JP, Shaw GM, Hahn BH, Doms RW: Transmitted/founder and chronic HIV-1 envelope proteins are distinguished by differential utilization of CCR5. J Virol 2013, 87:2401-2411.
• [81]Lee B, Sharron M, Blanpain C, Doranz BJ, Vakili J, Setoh P, Berg E, Liu G, Guy HR, Durell SR, Parmentier M, Chang CN, Price K, Tsang M, Doms RW: Epitope mapping of CCR5 reveals multiple conformational states and distinct but overlapping structures involved in chemokine and coreceptor function. J Biol Chem 1999, 274:9617-9626.
• [82]Berro R, Klasse PJ, Lascano D, Flegler A, Nagashima KA, Sanders RW, Sakmar TP, Hope TJ, Moore JP: Multiple CCR5 conformations on the cell surface are used differentially by human immunodeficiency viruses resistant or sensitive to CCR5 inhibitors. J Virol 2011, 85:8227-8240.
• [83]Thiele S, Steen A, Jensen PC, Mokrosinski J, Frimurer TM, Rosenkilde MM: Allosteric and orthosteric sites in CC chemokine receptor (CCR5), a chimeric receptor approach. J Biol Chem 2011, 286:37543-37554.
• [84]Baribaud F, Edwards TG, Sharron M, Brelot A, Heveker N, Price K, Mortari F, Alizon M, Tsang M, Doms RW: Antigenically distinct conformations of CXCR4. J Virol 2001, 75:8957-8967.
• [85]Nakano Y, Monde K, Terasawa H, Yuan Y, Yusa K, Harada S, Maeda Y: Preferential recognition of monomeric CCR5 expressed in cultured cells by the HIV-1 envelope glycoprotein gp120 for the entry of R5 HIV-1. Virology 2014, 452–453:117-124.
• [86]Fenyö EM, Esbjörnsson J, Medstrand P, Jansson M: Human immunodeficiency virus type 1 biological variation and coreceptor use: From concept to clinical significance. J Intern Med 2011, 270:520-531.
• [87]Flegler AJ, Cianci GC, Hope TJ: CCR5 conformations are dynamic and modulated by localization, trafficking and G protein association. PLoS One 2014, 9:e89056.
• [88]Ketas TJ, Kuhmann SE, Palmer A, Zurita J, He W, Ahuja SK, Klasse PJ, Moore JP: Cell surface expression of CCR5 and other host factors influence the inhibition of HIV-1 infection of human lymphocytes by CCR5 ligands. Virology 2007, 364:281-290.
• [89]Melikyan GB, Platt EJ, Kabat D: The role of the N-terminal segment of CCR5 in HIV-1 Env-mediated membrane fusion and the mechanism of virus adaptation to CCR5 lacking this segment. Retrovirology 2007, 4:55.
• [90]Wu L, LaRosa G, Kassam N, Gordon C, Heath H, Ruffing N, Chen H, Humblias J, Samson M, Parmentier M, Moore JP, Mackay CR: Interaction of chemokine receptor CCR5 with its ligands: multiple domains for HIV-1 gp120 binding and a single domain for chemokine binding. J Exp Med 1997, 186:8.
• [91]Nedellec R, Coetzer M, Shimizu N, Hoshino H, Polonis VR, Morris L, Martensson UE, Binley J, Overbaugh J, Mosier DE: Virus entry via the alternative coreceptors CCR3 and FPRL1 differs by human immunodeficiency virus type 1 subtype. J Virol 2009, 83:8353-8363.
• [92]Cashin K, Jakobsen MR, Sterjovski J, Roche M, Ellett A, Flynn JK, Borm K, Gouillou M, Churchill MJ, Gorry PR: Linkages between HIV-1 specificity for CCR5 or CXCR4 and in vitro usage of alternative coreceptors during progressive HIV-1 subtype C infection. Retrovirology 2013, 10:98.
• [93]Renjifo B, Gilbert P, Chaplin B, Msamanga G, Mwakagile D, Fawzi W, Essex M: Preferential in-utero transmission of HIV-1 subtype C as compared to HIV-1 subtype A or D. AIDS 2004, 18:1629-1636.
• [94]Abraha A, Nankya IL, Gibson R, Demers K, Tebit DM, Johnston E, Katzenstein D, Siddiqui A, Herrera C, Fischetti L, Shattock RJ, Arts EJ: CCR5- and CXCR4-tropic subtype C human immunodeficiency virus type 1 isolates have a lower level of pathogenic fitness than other dominant group M subtypes: implications for the epidemic. J Virol 2009, 83:5592-5605.
• [95]Ball SC, Abraha A, Collins KR, Marozsan AJ, Baird H, Quinones-Mateu ME, Penn-Nicholson A, Murray M, Richard N, Lobritz M, Zimmerman PA, Kawamura T, Blauvelt A, Arts EJ: Comparing the ex vivo fitness of CCR5-tropic human immunodeficiency virus type 1 isolates of subtypes B and C. J Virol 2003, 77:1021-1038.
• [96]Marozsan AJ, Moore DM, Lobritz MA, Fraundorf E, Abraha A, Reeves JD, Arts EJ: Differences in the fitness of Two diverse wild-type human immunodeficiency virus type 1 isolates Are related to the efficiency of cell binding and entry. J Virol 2005, 79:7121-7134.
• [97]Morner A, Bjorndal A, Albert J, Kewalramani VN, Littman DR, Inoue R, Thorstensson R, Fenyo EM, Bjorling E: Primary human immunodeficiency virus type 2 (HIV-2) isolates, like HIV-1 isolates, frequently use CCR5 but show promiscuity in coreceptor usage. J Virol 1999, 73:2343-2349.