Abstract
A transmission bottleneck occurs during each human immunodeficiency virus (HIV) transmission event, which allows only a few viruses to establish new infection. However, the genetic characteristics of the transmitted viruses that are preferentially selected have not been fully elucidated. Here, we analyzed amino acids changes in the envelope protein during simian immunodeficiency virus (SIV)/HIV deep transmission history and current HIV evolution within the last 15–20 years. Our results confirmed that the V1V2 region of gp120 protein, particularly V1, was preferentially selected. A shorter V1 region was preferred during transmission history, while during epidemic, HIV may evolve to an expanded V1 region gradually and thus escape immune recognition. We then constructed different HIV-1 V1 mutants using different HIV-1 subtypes to elucidate the role of the V1 region in envelope function. We found that the V1 region, although highly variable, was indispensable for virus entry and infection, probably because V1 deletion mutants exhibited impaired processing of gp160 into mature gp120 and gp41. Additionally, the V1 region affected Env incorporation. These results indicated that the V1 region played a critical role in HIV transmission and infection.
References
Alkhatib G, Combadiere C, Broder CC, Feng Y, Kennedy PE, Murphy PM, Berger EA. 1996. CC CKRS: A RANTES, MIP-1 alpha, MIP-1 beta receptor as a fusion cofactor for macrophagetropic HIV-1. Science, 272: 1955–1958.
Boeras DI, Hraber PT, Hurlston M, Evans-Strickfaden T, Bhattacharya T, Giorgi EE, Mulenga J, Karita E, Korber BT, Allen S, Hart CE, Derdeyn CA, Hunter E. 2011. Role of donor genital tract HIV-1 diversity in the transmission bottleneck. Proc Natl Acad Sci U S A, 108: E1156–E1163.
Bunnik EM, Euler Z, Welkers MR, Boeser-Nunnink BD, Grijsen ML, Prins JM, Schuitemaker H. 2010. Adaptation of HIV-1 envelope gp120 to humoral immunity at a population level. Nat Med, 16: 995–997.
Cardaci S, Soster M, Bussolino F, Marchio S. 2013. The V1/V2 loop of HIV-1 gp120 is necessary for Tat binding and consequent modulation of virus entry. FEBS Lett, 587: 2943–2951.
Carlson JM, Schaefer M, Monaco DC, Batorsky R, Claiborne DT, Prince J, Deymier MJ, Ende ZS, Klatt NR, DeZiel CE, Lin TH, Peng J, Seese AM, Shapiro R, Frater J, Ndung'u T, Tang J, Goepfert P, Gilmour J, Price MA, Kilembe W, Heckerman D, Goulder PJ, Allen TM, Allen S, Hunter E. 2014. HIV transmission. Selection bias at the heterosexual HIV-1 transmission bottleneck. Science, 345: 1254031.
Cavrois M, Neidleman J, Santiago ML, Derdeyn CA, Hunter E, Greene WC. 2014. Enhanced fusion and virion incorporation for HIV-1 subtype C envelope glycoproteins with compact V1/V2 domains. J Virol, 88: 2083–2094.
Chohan B, Lang D, Sagar M, Korber B, Lavreys L, Richardson B, Overbaugh J. 2005. Selection for human immunodeficiency virus type 1 envelope glycosylation variants with shorter V1-V2 loop sequences occurs during transmission of certain genetic subtypes and may impact viral RNA levels. J Virol, 79: 6528–6531.
Curlin ME, Zioni R, Hawes SE, Liu Y, Deng W, Gottlieb GS, Zhu T, Mullins JI. 2010. HIV-1 envelope subregion length variation during disease progression. PLoS Pathog, 6: e1001228.
Dalgleish AG, Beverley PC, Clapham PR, Crawford DH, Greaves MF, Weiss RA. 1984. The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus. Nature, 312: 763–767.
Dang S, Wang Y, Budeus B, Verheyen J, Yang R, Hoffmann D. 2014. Differential selection in HIV-1 gp120 between subtype B and East Asian variant B'. Virol Sin, 29: 40–47.
Del Prete GQ, Ailers B, Moldt B, Keele BF, Estes JD, Rodriguez A, Sampias M, Oswald K, Fast R, Trubey CM, Chertova E, Smedley J, LaBranche CC, Montefiori DC, Burton DR, Shaw GM, Markowitz M, Piatak M, Jr., KewalRamani VN, Bieniasz PD, Lifson JD, Hatziioannou T. 2014. Selection of unadapted, pathogenic SHIVs encoding newly transmitted HIV-1 envelope proteins. Cell Host Microbe, 16: 412–418.
Deng HK, Liu R, Ellmeier W, Choe S, Unutmaz D, Burkhart M, DiMarzio P, Marmon S, Sutton RE, Hill CM, Davis CB, Peiper SC, Schall TJ, Littman DR, Landau NR. 1996. Identification of a major co-receptor for primary isolates of HIV-1. Nature, 381: 661–666.
Feng Y, Broder CC, Kennedy PE, Berger EA. 1996. HIV-1 entry cofactor: Functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor. Science, 272: 872–877.
Frange P, Meyer L, Jung M, Goujard C, Zucman D, Abel S, Hochedez P, Gousset M, Gascuel O, Rouzioux C, Chaix ML, Group APCS. 2013. Sexually-transmitted/founder HIV-1 cannot be directly predicted from plasma or PBMC-derived viral quasispecies in the transmitting partner. PLoS One, 8: e69144.
Gonzalez MW, DeVico AL, Lewis GK, Spouge JL. 2015. Conserved molecular signatures in gp120 are associated with the genetic bottleneck during simian immunodeficiency virus (SIV), SIV-human immunodeficiency virus (SHIV), and HIV type 1 (HIV-1) transmission. J Virol, 89: 3619–3629.
Hamoudi M, Simon-Loriere E, Gasser R, Negroni M. 2013. Genetic diversity of the highly variable V1 region interferes with Human Immunodeficiency Virus type 1 envelope functionality. Retrovirology, 10: 114.
Ishikawa H, Meng FX, Kondo N, Iwamoto A, Matsuda Z. 2012. Generation of a dual-functional split-reporter protein for monitoring membrane fusion using self-associating split GFP. Protein Eng Des Sel, 25: 813–820.
Joseph SB, Swanstrom R. 2014. HIV/AIDS. A fitness bottleneck in HIV-1 transmission. Science, 345: 136–137.
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, Wood N, Seoighe C, Perelson AS, Bhattacharya T, Korber BT, Hahn BH, Shaw GM. 2008. Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection. Proc Natl Acad Sci U S A, 105: 7552–7557.
Klasse PJ. 2012. The molecular basis of HIV entry. Cell Microbiol, 14: 1183–1192.
Kondo N, Miyauchi K, Meng FX, Iwamoto A, Matsuda Z. 2010. Conformational Changes of the HIV-1 Envelope Protein during Membrane Fusion Are Inhibited by the Replacement of Its Membrane-spanning Domain. J Biol Chem, 285: 14681–14688.
Li Y, Yang D, Wang JY, Yao Y, Zhang WZ, Wang LJ, Cheng DC, Yang FK, Zhang FM, Zhuang M, Ling H. 2014. Critical amino acids within the human immunodeficiency virus type 1 envelope glycoprotein V4 N- and C-terminals contribute to virus entry. PLoS One, 9: e86083.
Liao HX, Lynch R, Zhou T, Gao F, Alam SM, Boyd SD, Fire AZ, Roskin KM, Schramm CA, Zhang Z, Zhu J, Shapiro L, Program NCS, Mullikin JC, Gnanakaran S, Hraber P, Wiehe K, Kelsoe G, Yang G, Xia SM, Montefiori DC, Parks R, Lloyd KE, Scearce RM, Soderberg KA, Cohen M, Kamanga G, Louder MK, Tran LM, Chen Y, Cai F, Chen S, Moquin S, Du X, Joyce MG, Srivatsan S, Zhang B, Zheng A, Shaw GM, Hahn BH, Kepler TB, Korber BT, Kwong PD, Mascola JR, Haynes BF. 2013a. Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus. Nature, 496: 469–476.
Liao HX, Tsao CY, Alam SM, Muldoon M, Vandergrift N, Ma BJ, Lu XZ, Sutherland LL, Scearce RM, Bowman C, Parks R, Chen HY, Blinn JH, Lapedes A, Watson S, Xia SM, Foulger A, Hahn BH, Shaw GM, Swanstrom R, Montefiori DC, Gao F, Haynes BF, Korber B. 2013b. Antigenicity and Immunogenicity of Transmitted/Founder, Consensus, and Chronic Envelope Glycoproteins of Human Immunodeficiency Virus Type 1. J Virol, 87: 4185–4201.
Nie J, Zhao J, Chen Q, Huang W, Wang Y. 2014. Three amino acid residues in the envelope of human immunodeficiency virus type 1 CRF07_BC regulate viral neutralization susceptibility to the human monoclonal neutralizing antibody IgG1b12. Virol Sin, 29: 299–307.
O'Connell RJ, Kim JH, Excler JL. 2014. The HIV-1 gp120 V1V2 loop: structure, function and importance for vaccine development. Expert Rev Vaccines, 13: 1489–1500.
Parrish NF, Gao F, Li H, Giorgi EE, Barbian HJ, Parrish EH, Zajic L, Iyer SS, Decker JM, Kumar A, Hora B, Berg A, Cai FP, Hopper J, Denny TN, Ding HT, Ochsenbauer C, Kappes JC, Galimidi RP, West AP, Bjorkman PJ, Wilen CB, Doms RW, O'Brien M, Bhardwaj N, Borrow P, Haynes BF, Muldoon M, Theiler JP, Korber B, Shaw GM, Hahn BH. 2013. Phenotypic properties of transmitted founder HIV-1. Proc Natl Acad Sci U S A, 110: 6626–6633.
Pollakis G, Baan E, van Werkhoven MB, Berkhout B, Bakker M, Jurriaans S, Paxton WA. 2015. Association between gp120 envelope V1V2 and V4V5 variable loop profiles in a defined HIV-1 transmission cluster. AIDS, 29: 1161–1171.
Sagar M, Laeyendecker O, Lee S, Gamiel J, Wawer MJ, Gray RH, Serwadda D, Sewankambo NK, Shepherd JC, Toma J, Huang W, Quinn TC. 2009. Selection of HIV variants with signature genotypic characteristics during heterosexual transmission. J Infect Dis, 199: 580–589.
Sagar M, Wu X, Lee S, Overbaugh J. 2006. Human immunodeficiency virus type 1 V1-V2 envelope loop sequences expand and add glycosylation sites over the course of infection, and these modifications affect antibody neutralization sensitivity. J Virol, 80: 9586–9598.
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, Shaw GM. 2009. Genetic identity, biological phenotype, and evolutionary pathways of transmitted/founder viruses in acute and early HIV-1 infection. J Exp Med, 206: 1273–1289.
Samleerat T, Braibant M, Jourdain G, Moreau A, Ngo-Giang-Huong N, Leechanachai P, Hemvuttiphan J, Hinjiranandana T, Changchit T, Warachit B, Suraseranivong V, Lallemant M, Barin F. 2008. Characteristics of HIV type 1 (HIV-1) glycoprotein 120 env sequences in mother-infant pairs infected with HIV-1 subtype CRF01_AE. J Infect Dis, 198: 868–876.
Sharp PM, Hahn BH. 2011. Origins of HIV and the AIDS pandemic. Cold Spring Harb Perspect Med, 1: a006841.
Sharp PM, Rayner JC, Hahn BH. 2013. Evolution. Great apes and zoonoses. Science, 340: 284–286.
Shaw GM, Hunter E. 2012. HIV transmission. Cold Spring Harb Perspect Med, 2: a006965.
Starcich BR, Hahn BH, Shaw GM, Mcneely PD, Modrow S, Wolf H, Parks ES, Parks WP, Josephs SF, Gallo RC, Wongstaal F. 1986. Identification and Characterization of Conserved and Variable Regions in the Envelope Gene of Htlv-Iii Lav, the Retrovirus of Aids. Cell, 45: 637–648.
Stone M, Keele BF, Ma ZM, Bailes E, Dutra J, Hahn BH, Shaw GM, Miller CJ. 2010. A limited number of simian immunodeficiency virus (SIV) env variants are transmitted to rhesus macaques vaginally inoculated with SIVmac251. J Virol, 84: 7083–7095.
van Gils MJ, Bunnik EM, Boeser-Nunnink BD, Burger JA, Terlouw-Klein M, Verwer N, Schuitemaker H. 2011. Longer V1V2 region with increased number of potential N-linked glycosylation sites in the HIV-1 envelope glycoprotein protects against HIV-specific neutralizing antibodies. J Virol, 85: 6986–6995.
Wang H, Li X, Nakane S, Liu S, Ishikawa H, Iwamoto A, Matsuda Z. 2014. Co-Expression of Foreign Proteins Tethered to HIV-1 Envelope Glycoprotein on the Cell Surface by Introducing an Intervening Second Membrane-Spanning Domain. Plos One, 9: e96790.
Wang J, Sen J, Rong L, Caffrey M. 2008. Role of the HIV gp120 conserved domain 1 in processing and viral entry. J Biol Chem, 283: 32644–32649.
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. 2011. Phenotypic and immunologic comparison of clade B transmitted/founder and chronic HIV-1 envelope glycoproteins. J Virol, 85: 8514–8527.
Willey RL, Rutledge RA, Dias S, Folks T, Theodore T, Buckler CE, Martin MA. 1986. Identification of Conserved and Divergent Domains within the Envelope Gene of the Acquired-Immunodeficiency-Syndrome Retrovirus. Proc Natl Acad Sci U S A, 83: 5038–5042.
Worobey M, Telfer P, Souquiere S, Hunter M, Coleman CA, Metzger MJ, Reed P, Makuwa M, Hearn G, Honarvar S, Roques P, Apetrei C, Kazanji M, Marx PA. 2010. Island biogeography reveals the deep history of SIV. Science, 329: 1487.
Yuan T, Li J, Zhang MY. 2013. HIV-1 envelope glycoprotein variable loops are indispensable for envelope structural integrity and virus entry. PLoS One, 8: e69789.
Author information
Authors and Affiliations
Corresponding authors
Additional information
ORCID: 0000-0002-6333-7941
ORCID: 0000-0002-3060-9867
Rights and permissions
About this article
Cite this article
Li, Y., Dittmer, U., Wang, Y. et al. The V1 region of gp120 is preferentially selected during SIV/HIV transmission and is indispensable for envelope function and virus infection. Virol. Sin. 31, 207–218 (2016). https://doi.org/10.1007/s12250-016-3725-5
Received:
Revised:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12250-016-3725-5
Keywords
- simian immunodeficiency virus (SIV)
- human immunodeficiency virus (HIV)
- transmission
- selection
- V1 loop
- Env function