Differential glycosylation of envelope gp120 is associated with differential recognition of HIV-1 by virus-specific antibodies and cell infection
Status PubMed-not-MEDLINE Jazyk angličtina Země Anglie, Velká Británie Médium electronic-ecollection
Typ dokumentu časopisecké články
PubMed
25120578
PubMed Central
PMC4130436
DOI
10.1186/1742-6405-11-23
PII: 1742-6405-11-23
Knihovny.cz E-zdroje
- Klíčová slova
- Deglycosylation resistance, Glycan-specific antibody, Neutralization inhibition, gp120 glycosylation,
- Publikační typ
- časopisecké články MeSH
BACKGROUND: HIV-1 entry into host cells is mediated by interactions between the virus envelope glycoprotein (gp120/gp41) and host-cell receptors. N-glycans represent approximately 50% of the molecular mass of gp120 and serve as potential antigenic determinants and/or as a shield against immune recognition. We previously reported that N-glycosylation of recombinant gp120 varied, depending on the producer cells, and the glycosylation variability affected gp120 recognition by serum antibodies from persons infected with HIV-1 subtype B. However, the impact of gp120 differential glycosylation on recognition by broadly neutralizing monoclonal antibodies or by polyclonal antibodies of individuals infected with other HIV-1 subtypes is unknown. METHODS: Recombinant multimerizing gp120 antigens were expressed in different cells, HEK 293T, T-cell, rhabdomyosarcoma, hepatocellular carcinoma, and Chinese hamster ovary cell lines. Binding of broadly neutralizing monoclonal antibodies and polyclonal antibodies from sera of subtype A/C HIV-1-infected subjects with individual gp120 glycoforms was assessed by ELISA. In addition, immunodetection was performed using Western and dot blot assays. Recombinant gp120 glycoforms were tested for inhibition of infection of reporter cells by SF162 and YU.2 Env-pseudotyped R5 viruses. RESULTS: We demonstrated, using ELISA, that gp120 glycans sterically adjacent to the V3 loop only moderately contribute to differential recognition of a short apex motif GPGRA and GPGR by monoclonal antibodies F425 B4e8 and 447-52D, respectively. The binding of antibodies recognizing longer peptide motifs overlapping with GPGR epitope (268 D4, 257 D4, 19b) was significantly altered. Recognition of gp120 glycoforms by monoclonal antibodies specific for other than V3-loop epitopes was significantly affected by cell types used for gp120 expression. These epitopes included CD4-binding site (VRC03, VRC01, b12), discontinuous epitope involving V1/V2 loop with the associated glycans (PG9, PG16), and an epitope including V3-base-, N332 oligomannose-, and surrounding glycans-containing epitope (PGT 121). Moreover, the different gp120 glycoforms variably inhibited HIV-1 infection of reporter cells. CONCLUSION: Our data support the hypothesis that the glycosylation machinery of different cells shapes gp120 glycosylation and, consequently, impacts envelope recognition by specific antibodies as well as the interaction of HIV-1 gp120 with cellular receptors. These findings underscore the importance of selection of appropriately glycosylated HIV-1 envelope as a vaccine antigen.
Department of Immunology Palacky University in Olomouc 77100 Olomouc Czech Republic
Department of Microbiology University of Alabama at Birmingham Birmingham AL 35294 USA
Department of Surgery University of Alabama at Birmingham Birmingham AL 35294 USA
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Kwong PD, Wyatt R, Robinson J, Sweet RW, Sodroski J, Hendrickson WA. Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody. Nature. 1998;393:648–659. PubMed PMC
Wyatt R, Kwong PD, Desjardins E, Sweet RW, Robinson J, Hendrickson WA, Sodroski JG. The antigenic structure of the HIV gp120 envelope glycoprotein. Nature. 1998;393:705–711. PubMed
Pantophlet R, Burton DR. gp120: target for neutralizing HIV-1 antibodies. Annu Rev Immunol. 2006;24:739–769. PubMed
Wei X, Decker JM, Wang S, Hui H, Kappes JC, Wu X, Salazar-Gonzalez JF, Salazar MG, Kilby JM, Saag MS, Komarova NL, Nowak MA, Hahn BH, Kwong PD, Shaw GM. Antibody neutralization and escape by HIV-1. Nature. 2003;422:307–312. PubMed
Arthos J, Cicala C, Martinelli E, Macleod K, Van Ryk D, Wei D, Xiao Z, Veenstra TD, Conrad TP, Lempicki RA, McLaughlin S, Pascuccio M, Gopaul R, McNally J, Cruz CC, Censoplano N, Chung E, Reitano KN, Kottilil S, Goode DJ, Fauci AS. HIV-1 envelope protein binds to and signals through integrin alpha4beta7, the gut mucosal homing receptor for peripheral T cells. Nat Immunol. 2008;9:301–309. PubMed
Cicala C, Martinelli E, McNally JP, Goode DJ, Gopaul R, Hiatt J, Jelicic K, Kottilil S, Macleod K, O’Shea A, Patel N, Van Ryk D, Wei D, Pascuccio M, Yi L, McKinnon L, Izulla P, Kimani J, Kaul R, Fauci AS, Arthos J. The integrin alpha4beta7 forms a complex with cell-surface CD4 and defines a T-cell subset that is highly susceptible to infection by HIV-1. Proc Natl Acad Sci U S A. 2009;106:20877–20882. PubMed PMC
Hioe CE, Bastiani L, Hildreth JE, Zolla-Pazner S. Role of cellular adhesion molecules in HIV type 1 infection and their impact on virus neutralization. AIDS Res Hum Retroviruses. 1998;14(Suppl 3):S247–S254. PubMed
Hioe CE, Hildreth JE, Zolla-Pazner S. Enhanced HIV type 1 neutralization by human anti-glycoprotein 120 monoclonal antibodies in the presence of monoclonal antibodies to lymphocyte function-associated molecule 1. AIDS Res Hum Retroviruses. 1999;15:523–531. PubMed
Simek MD, Rida W, Priddy FH, Pung P, Carrow E, Laufer DS, Lehrman JK, Boaz M, Tarragona-Fiol T, Miiro G, Birungi J, Pozniak A, McPhee DA, Manigart O, Karita E, Inwoley A, Jaoko W, DeHovitz J, Bekker L-G, Pitisuttithum P, Paris R, Walker LM, Poignard P, Wrin T, Fast PE, Burton DR, Koff WC. Human immunodeficiency virus type 1 elite neutralizers: individuals with broad and potent neutralizing activity identified by using a high-throughput neutralization assay together with an analytical selection algorithm. J Virol. 2009;83:7337–7348. PubMed PMC
Doria-Rose NA, Klein RM, Manion MM, O’Dell S, Phogat A, Chakrabarti B, Hallahan CW, Migueles SA, Wrammert J, Ahmed R, Nason M, Wyatt RT, Mascola JR, Connors M. Frequency and phenotype of human immunodeficiency virus envelope-specific B cells from patients with broadly cross-neutralizing antibodies. J Virol. 2009;83:188–199. PubMed PMC
Walker LM, Simek MD, Priddy F, Gach JS, Wagner D, Zwick MB, Phogat SK, Poignard P, Burton DR. A limited number of antibody specificities mediate broad and potent serum neutralization in selected HIV-1 infected individuals. PLoS Pathog. 2010;6:e1001028. PubMed PMC
Stamatatos L, Morris L, Burton DR, Mascola JR. Neutralizing antibodies generated during natural HIV-1 infection: good news for an HIV-1 vaccine? Nat Med. 2009;15:866–870. PubMed
Fauci AS. 25 years of HIV. Nature. 2008;453:289–290. PubMed
Balzarini J. Targeting the glycans of gp120: a novel approach aimed at the Achilles heel of HIV. Lancet Infect Dis. 2005;5:726–731. PubMed
Letvin NL, Rao SS, Dang V, Buzby AP, Korioth-Schmitz B, Dombagoda D, Parvani JG, Clarke RH, Bar L, Carlson KR, Kozlowski PA, Hirsch VM, Mascola JR, Nabel GJ. No evidence for consistent virus-specific immunity in simian immunodeficiency virus-exposed, uninfected rhesus monkeys. J Virol. 2007;81:12368–12374. PubMed PMC
Robinson HL. HIV/AIDS vaccines: 2007. Clin Pharmacol Ther. 2007;82:686–693. PubMed
Zhu X, Borchers C, Bienstock RJ, Tomer KB. Mass spectrometric characterization of the glycosylation pattern of HIV-gp120 expressed in CHO cells. Biochemistry. 2000;39:11194–11204. PubMed
Go EP, Chang Q, Liao HX, Sutherland LL, Alam SM, Haynes BF, Desaire H. Glycosylation site-specific analysis of clade C HIV-1 envelope proteins. J Proteome Res. 2009;8:4231–4242. PubMed PMC
Go EP, Hewawasam G, Liao HX, Chen H, Ping LH, Anderson JA, Hua DC, Haynes BF, Desaire H. Characterization of glycosylation profiles of HIV-1 transmitted/founder envelopes by mass spectrometry. J Virol. 2011;85:8270–8284. PubMed PMC
Raska M, Novak J. Involvement of envelope-glycoprotein glycans in HIV-1 biology and infection. Arch Immunol Ther Exp (Warsz) 2010;58:191–208. PubMed
Raska M, Takahashi K, Czernekova L, Zachova K, Hall S, Moldoveanu Z, Elliot MC, Wilson L, Brown R, Jancova D, Barnes S, Vrbkova J, Tomana M, Smith PD, Mestecky J, Renfrow MB, Novak J. Glycosylation patterns of HIV-1 gp120 depend on the type of expressing cells and affect antibody recognition. J Biol Chem. 2010;285:20860–20869. PubMed PMC
Mizuochi T, Matthews TJ, Kato M, Hamako J, Titani K, Solomon J, Feizi T. Diversity of oligosaccharide structures on the envelope glycoprotein gp120 of human immunodeficiency virus 1 from the lymphoblastoid cell line H9. Presence of complex-type oligosaccharides with bisecting N-acetylglucosamine residues. J Biol Chem. 1990;265:8519–8524. PubMed
Mizuochi T, Spellman MW, Larkin M, Solomon J, Basa LJ, Feizi T. Structural characterization by chromatographic profiling of the oligosaccharides of human immunodeficiency virus (HIV) recombinant envelope glycoprotein gp120 produced in Chinese hamster ovary cells. Biomed Chromatogr. 1988;2:260–270. PubMed
Mizuochi T, Spellman MW, Larkin M, Solomon J, Basa LJ, Feizi T. Carbohydrate structures of the human-immunodeficiency-virus (HIV) recombinant envelope glycoprotein gp120 produced in Chinese-hamster ovary cells. Biochem J. 1988;254:599–603. PubMed PMC
Reitter JN, Means RE, Desrosiers RC. A role for carbohydrates in immune evasion in AIDS. Nat Med. 1998;4:679–684. PubMed
Reitter JN, Desrosiers RC. Identification of replication-competent strains of simian immunodeficiency virus lacking multiple attachment sites for N-linked carbohydrates in variable regions 1 and 2 of the surface envelope protein. J Virol. 1998;72:5399–5407. PubMed PMC
Ho YS, Abecasis AB, Theys K, Deforche K, Dwyer DE, Charleston M, Vandamme AM, Saksena NK. HIV-1 gp120 N-linked glycosylation differs between plasma and leukocyte compartments. Virol J. 2008;5:14. PubMed PMC
Go EP, Irungu J, Zhang Y, Dalpathado DS, Liao HX, Sutherland LL, Alam SM, Haynes BF, Desaire H. Glycosylation site-specific analysis of HIV envelope proteins (JR-FL and CON-S) reveals major differences in glycosylation site occupancy, glycoform profiles, and antigenic epitopes’ accessibility. J Proteome Res. 2008;7:1660–1674. PubMed PMC
Clapham PR, McKnight A. HIV-1 receptors and cell tropism. Br Med Bull. 2001;58:43–59. PubMed
Cicala C, Arthos J, Fauci AS. HIV-1 envelope, integrins and co-receptor use in mucosal transmission of HIV. J Transl Med. 2011;9(Suppl 1):S2. PubMed PMC
Decker JM, Bibollet-Ruche F, Wei X, Wang S, Levy DN, Wang W, Delaporte E, Peeters M, Derdeyn CA, Allen S, Hunter E, Saag MS, Hoxie JA, Hahn BH, Kwong PD, Robinson JE, Shaw GM. Antigenic conservation and immunogenicity of the HIV coreceptor binding site. J Exp Med. 2005;201:1407–1419. PubMed PMC
Salazar-Gonzalez JF, Bailes E, Pham KT, Salazar MG, Guffey MB, Keele BF, 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. PubMed PMC
Pollakis G, Kang S, Kliphuis A, Chalaby MI, Goudsmit J, Paxton WA. N-linked glycosylation of the HIV type-1 gp120 envelope glycoprotein as a major determinant of CCR5 and CXCR4 coreceptor utilization. J Biol Chem. 2001;276:13433–13441. PubMed
McCaffrey RA, Saunders C, Hensel M, Stamatatos L. N-linked glycosylation of the V3 loop and the immunologically silent face of gp120 protects human immunodeficiency virus type 1 SF162 from neutralization by anti-gp120 and anti-gp41 antibodies. J Virol. 2004;78:3279–3295. PubMed PMC
Clevestig P, Pramanik L, Leitner T, Ehrnst A. CCR5 use by human immunodeficiency virus type 1 is associated closely with the gp120 V3 loop N-linked glycosylation site. J Gen Virol. 2006;87:607–612. PubMed
Wolk T, Schreiber M. N-Glycans in the gp120 V1/V2 domain of the HIV-1 strain NL4-3 are indispensable for viral infectivity and resistance against antibody neutralization. Med Microbiol Immunol. 2006;195:165–172. PubMed
Huang X, Jin W, Hu K, Luo S, Du T, Griffin GE, Shattock RJ, Hu Q. Highly conserved HIV-1 gp120 glycans proximal to CD4-binding region affect viral infectivity and neutralizing antibody induction. Virology. 2012;423:97–106. PubMed
Rerks-Ngarm S, Pitisuttithum P, Nitayaphan S, Kaewkungwal J, Chiu J, Paris R, Premsri N, Namwat C, de Souza M, Adams E, Benenson M, Gurunathan S, Tartaglia J, McNeil JG, Francis DP, Stablein D, Birx DL, Chunsuttiwat S, Khamboonruang C, Thongcharoen P, Robb ML, Michael NL, Kunasol P, Kim JH. Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand. N Engl J Med. 2009;361:2209–2220. PubMed
Haynes BF, Gilbert PB, McElrath MJ, Zolla-Pazner S, Tomaras GD, Alam SM, Evans DT, Montefiori DC, Karnasuta C, Sutthent R, Liao HX, DeVico AL, Lewis GK, Williams C, Pinter A, Fong Y, Janes H, DeCamp A, Huang Y, Rao M, Billings E, Karasavvas N, Robb ML, Ngauy V, de Souza MS, Paris R, Ferrari G, Bailer RT, Soderberg KA, Andrews C. et al.Immune-correlates analysis of an HIV-1 vaccine efficacy trial. N Engl J Med. 2012;366:1275–1286. PubMed PMC
Doores KJ, Burton DR. Variable loop glycan dependency of the broad and potent HIV-1-neutralizing antibodies PG9 and PG16. J Virol. 2010;84:10510–10521. PubMed PMC
Walker LM, Huber M, Doores KJ, Falkowska E, Pejchal R, Julien JP, Wang SK, Ramos A, Chan-Hui PY, Moyle M, Mitcham JL, Hammond PW, Olsen OA, Phung P, Fling S, Wong CH, Phogat S, Wrin T, Simek MD, Koff WC, Wilson IA, Burton DR, Poignard P. Broad neutralization coverage of HIV by multiple highly potent antibodies. Nature. 2011;477:466–470. PubMed PMC
Kwong PD, Mascola JR, Nabel GJ. The changing face of HIV vaccine research. Journal of the International Aids Society. 2012;15:17407. PubMed PMC
Platt EJ, Gomes MM, Kabat D. Kinetic mechanism for HIV-1 neutralization by antibody 2G12 entails reversible glycan binding that slows cell entry. Proc Natl Acad Sci U S A. 2012;109:7829–7834. PubMed PMC
Pejchal R, Doores KJ, Walker LM, Khayat R, Huang PS, Wang SK, Stanfield RL, Julien JP, Ramos A, Crispin M, Depetris R, Katpally U, Marozsan A, Cupo A, Maloveste S, Liu Y, McBride R, Ito Y, Sanders RW, Ogohara C, Paulson JC, Feizi T, Scanlan CN, Wong CH, Moore JP, Olson WC, Ward AB, Poignard P, Schief WR, Burton DR. et al.A potent and broad neutralizing antibody recognizes and penetrates the HIV glycan shield. Science. 2011;334:1097–1103. PubMed PMC
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, 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. PubMed PMC
Pejchal R, Walker LM, Stanfield RL, Phogat SK, Koff WC, Poignard P, Burton DR, Wilson IA. Structure and function of broadly reactive antibody PG16 reveal an H3 subdomain that mediates potent neutralization of HIV-1. Proc Natl Acad Sci U S A. 2010;107:11483–11488. PubMed PMC
Julien JP, Sok D, Khayat R, Lee JH, Doores KJ, Walker LM, Ramos A, Diwanji DC, Pejchal R, Cupo A, Katpally U, Depetris RS, Stanfield RL, McBride R, Marozsan AJ, Paulson JC, Sanders RW, Moore JP, Burton DR, Poignard P, Ward AB, Wilson IA. Broadly neutralizing antibody PGT121 allosterically modulates CD4 binding via recognition of the HIV-1 gp120 V3 base and multiple surrounding glycans. PLoS Pathog. 2013;9:e1003342. PubMed PMC
Calarese DA, Scanlan CN, Zwick MB, Deechongkit S, Mimura Y, Kunert R, Zhu P, Wormald MR, Stanfield RL, Roux KH, Kelly JW, Rudd PM, Dwek RA, Katinger H, Burton DR, Wilson IA. Antibody domain exchange is an immunological solution to carbohydrate cluster recognition. Science. 2003;300:2065–2071. PubMed
Eggink D, Melchers M, Wuhrer M, van Montfort T, Dey AK, Naaijkens BA, David KB, Le Douce V, Deelder AM, Kang K, Olson WC, Berkhout B, Hokke CH, Moore JP, Sanders RW. Lack of complex N-glycans on HIV-1 envelope glycoproteins preserves protein conformation and entry function. Virology. 2010;401:236–247. PubMed PMC
Kong L, Sheppard NC, Stewart-Jones GB, Robson CL, Chen H, Xu X, Krashias G, Bonomelli C, Scanlan CN, Kwong PD, Jeffs SA, Jones IM, Sattentau QJ. Expression-system-dependent modulation of HIV-1 envelope glycoprotein antigenicity and immunogenicity. J Mol Biol. 2010;403:131–147. PubMed PMC
Gorny MK, Xu JY, Gianakakos V, Karwowska S, Williams C, Sheppard HW, Hanson CV, Zolla-Pazner S. Production of site-selected neutralizing human monoclonal antibodies against the third variable domain of the human immunodeficiency virus type 1 envelope glycoprotein. Proc Natl Acad Sci U S A. 1991;88:3238–3242. PubMed PMC
Pantophlet R, Aguilar-Sino RO, Wrin T, Cavacini LA, Burton DR. Analysis of the neutralization breadth of the anti-V3 antibody F425-B4e8 and re-assessment of its epitope fine specificity by scanning mutagenesis. Virology. 2007;364:441–453. PubMed PMC
Gorny MK, Conley AJ, Karwowska S, Buchbinder A, Xu JY, Emini EA, Koenig S, Zolla-Pazner S. Neutralization of diverse human immunodeficiency virus type 1 variants by an anti-V3 human monoclonal antibody. J Virol. 1992;66:7538–7542. PubMed PMC
Burton DR, Barbas CF 3rd, Persson MA, Koenig S, Chanock RM, Lerner RA. A large array of human monoclonal antibodies to type 1 human immunodeficiency virus from combinatorial libraries of asymptomatic seropositive individuals. Proc Natl Acad Sci U S A. 1991;88:10134–10137. PubMed PMC
Pantophlet R, Wang M, Aguilar-Sino RO, Burton DR. The human immunodeficiency virus type 1 envelope spike of primary viruses can suppress antibody access to variable regions. J Virol. 2009;83:1649–1659. PubMed PMC
Bonomelli C, Doores KJ, Dunlop DC, Thaney V, Dwek RA, Burton DR, Crispin M, Scanlan CN. The glycan shield of HIV is predominantly oligomannose independently of production system or viral clade. PLoS One. 2011;6:e23521. PubMed PMC
Julien JP, Lee PS, Wilson IA. Structural insights into key sites of vulnerability on HIV-1 Env and influenza HA. Immunol Rev. 2012;250:180–198. PubMed PMC
Derdeyn CA, Decker JM, Bibollet-Ruche F, Mokili JL, Muldoon M, Denham SA, Heil ML, Kasolo F, Musonda R, Hahn BH, Shaw GM, Korber BT, Allen S, Hunter E. Envelope-constrained neutralization-sensitive HIV-1 after heterosexual transmission. Science. 2004;303:2019–2022. PubMed
Li H, Chien PC Jr, Tuen M, Visciano ML, Cohen S, Blais S, Xu CF, Zhang HT, Hioe CE. Identification of an N-linked glycosylation in the C4 region of HIV-1 envelope gp120 that is critical for recognition of neighboring CD4 T cell epitopes. J Immunol. 2008;180:4011–4021. PubMed
Kothe DL, Decker JM, Li Y, Weng Z, Bibollet-Ruche F, Zammit KP, Salazar MG, Chen Y, Salazar-Gonzalez JF, Moldoveanu Z, Mestecky J, Gao F, Haynes BF, Shaw GM, Muldoon M, Korber BT, Hahn BH. Antigenicity and immunogenicity of HIV-1 consensus subtype B envelope glycoproteins. Virology. 2007;360:218–234. PubMed PMC
Huang X, Barchi JJ Jr, Lung FD, Roller PP, Nara PL, Muschik J, Garrity RR. Glycosylation affects both the three-dimensional structure and antibody binding properties of the HIV-1IIIB GP120 peptide RP135. Biochemistry. 1997;36:10846–10856. PubMed
Wain LV, Bailes E, Bibollet-Ruche F, Decker JM, Keele BF, Van Heuverswyn F, Li Y, Takehisa J, Ngole EM, Shaw GM, Peeters M, Hahn BH, Sharp PM. Adaptation of HIV-1 to its human host. Mol Biol Evol. 2007;24:1853–1860. PubMed PMC
Reitz MS Jr, Hall L, Robert-Guroff M, Lautenberger J, Hahn BM, Shaw GM, Kong LI, Weiss SH, Waters D, Gallo RC, Blattner WA. Viral variability and serum antibody response in a laboratory worker infected with HIV type 1 (HTLV type IIIB) AIDS Res Hum Retroviruses. 1994;10:1143–1155. PubMed
Rong R, Gnanakaran S, Decker JM, Bibollet-Ruche F, Taylor J, Sfakianos JN, Mokili JL, Muldoon M, Mulenga J, Allen S, Hahn BH, Shaw GM, Blackwell JL, Korber BT, Hunter E, Derdeyn CA. Unique mutational patterns in the envelope alpha 2 amphipathic helix and acquisition of length in gp120 hypervariable domains are associated with resistance to autologous neutralization of subtype C human immunodeficiency virus type 1. J Virol. 2007;81:5658–5668. PubMed PMC
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. PubMed PMC
Burton DR, Ahmed R, Barouch DH, Butera ST, Crotty S, Godzik A, Kaufmann DE, McElrath MJ, Nussenzweig MC, Pulendran B, Scanlan CN, Schief WR, Silvestri G, Streeck H, Walker BD, Walker LM, Ward AB, Wilson IA, Wyatt R. A blueprint for HIV vaccine discovery. Cell Host Microbe. 2012;12:396–407. PubMed PMC
Koff WC. HIV vaccine development: challenges and opportunities towards solving the HIV vaccine-neutralizing antibody problem. Vaccine. 2012;30:4310–4315. PubMed
Moore PL, Gray ES, Wibmer CK, Bhiman JN, Nonyane M, Sheward DJ, Hermanus T, Bajimaya S, Tumba NL, Abrahams MR, Lambson BE, Ranchobe N, Ping L, Ngandu N, Abdool Karim Q, Abdool Karim SS, Swanstrom RI, Seaman MS, Williamson C, Morris L. Evolution of an HIV glycan-dependent broadly neutralizing antibody epitope through immune escape. Nat Med. 2012;18:1688–1692. PubMed PMC
Wang W, Nie J, Prochnow C, Truong C, Jia Z, Wang S, Chen XS, Wang Y. A systematic study of the N-glycosylation sites of HIV-1 envelope protein on infectivity and antibody-mediated neutralization . Retrovirology. 2013;10:14. PubMed PMC
Gorny MK, Xu JY, Karwowska S, Buchbinder A, Zolla-Pazner S. Repertoire of neutralizing human monoclonal antibodies specific for the V3 domain of HIV-1 gp120. J Immunol. 1993;150:635–643. PubMed
Bell CH, Pantophlet R, Schiefner A, Cavacini LA, Stanfield RL, Burton DR, Wilson IA. Structure of antibody F425-B4e8 in complex with a V3 peptide reveals a new binding mode for HIV-1 neutralization. J Mol Biol. 2008;375:969–978. PubMed PMC
Stanfield RL, Gorny MK, Williams C, Zolla-Pazner S, Wilson IA. Structural rationale for the broad neutralization of HIV-1 by human monoclonal antibody 447-52D. Structure. 2004;12:193–204. PubMed
Burke V, Williams C, Sukumaran M, Kim SS, Li H, Wang XH, Gorny MK, Zolla-Pazner S, Kong XP. Structural basis of the cross-reactivity of genetically related human anti-HIV-1 mAbs: implications for design of V3-based immunogens. Structure. 2009;17:1538–1546. PubMed PMC
Moore JP, Trkola A, Korber B, Boots LJ, Kessler JA 2nd, McCutchan FE, Mascola J, Ho DD, Robinson J, Conley AJ. A human monoclonal antibody to a complex epitope in the V3 region of gp120 of human immunodeficiency virus type 1 has broad reactivity within and outside clade B. J Virol. 1995;69:122–130. PubMed PMC
Scanlan CN, Pantophlet R, Wormald MR, Saphire EO, Calarese D, Stanfield R, Wilson IA, Katinger H, Dwek RA, Burton DR, Rudd PM. The carbohydrate epitope of the neutralizing anti-HIV-1 antibody 2G12. Adv Exp Med Biol. 2003;535:205–218. PubMed
Sanders RW, Venturi M, Schiffner L, Kalyanaraman R, Katinger H, Lloyd KO, Kwong PD, Moore JP. The mannose-dependent epitope for neutralizing antibody 2G12 on human immunodeficiency virus type 1 glycoprotein gp120. J Virol. 2002;76:7293–7305. PubMed PMC
Mouquet H, Scharf L, Euler Z, Liu Y, Eden C, Scheid JF, Halper-Stromberg A, Gnanapragasam PN, Spencer DI, Seaman MS, Schuitemaker H, Feizi T, Nussenzweig MC, Bjorkman PJ. Complex-type N-glycan recognition by potent broadly neutralizing HIV antibodies. Proc Natl Acad Sci U S A. 2012;109:E3268–E3277. PubMed PMC
Pancera M, Shahzad-Ul-Hussan S, Doria-Rose NA, McLellan JS, Bailer RT, Dai K, Loesgen S, Louder MK, Staupe RP, Yang Y, Zhang B, Parks R, Eudailey J, Lloyd KE, Blinn J, Alam SM, Haynes BF, Amin MN, Wang LX, Burton DR, Koff WC, Nabel GJ, Mascola JR, Bewley CA, Kwong PD. Structural basis for diverse N-glycan recognition by HIV-1-neutralizing V1-V2-directed antibody PG16. Nat Struct Mol Biol. 2013;20:804–813. PubMed PMC
Zhou T, Xu L, Dey B, Hessell AJ, Van Ryk D, Xiang SH, Yang X, Zhang MY, Zwick MB, Arthos J, Burton DR, Dimitrov DS, Sodroski J, Wyatt R, Nabel GJ, Kwong PD. Structural definition of a conserved neutralization epitope on HIV-1 gp120. Nature. 2007;445:732–737. PubMed PMC
Wu X, Zhou T, O’Dell S, Wyatt RT, Kwong PD, Mascola JR. Mechanism of human immunodeficiency virus type 1 resistance to monoclonal antibody B12 that effectively targets the site of CD4 attachment. J Virol. 2009;83:10892–10907. PubMed PMC
Wu X, Yang Z-Y, Li Y, Hogerkorp C-M, Schief WR, Seaman MS, Zhou T, Schmidt SD, Wu L, Xu L, Longo NS, McKee K, O'Dell S, Louder MK, Wycuff DL, Feng Y, Nason M, Doria-Rose N, Connors M, Kwong PD, Roederer M, Wyatt RT, Nabel GJ, Mascola JR. Rational Design of Envelope Identifies Broadly Neutralizing Human Monoclonal Antibodies to HIV-1. Science. 2010;329:856–861. PubMed PMC
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. PubMed PMC
Doores KJ, Fulton Z, Huber M, Wilson IA, Burton DR. Antibody 2G12 recognizes di-mannose equivalently in domain- and nondomain-exchanged forms but only binds the HIV-1 glycan shield if domain exchanged. J Virol. 2010;84:10690–10699. PubMed PMC
Crooks ET, Tong T, Osawa K, Binley JM. Enzyme digests eliminate nonfunctional Env from HIV-1 particle surfaces, leaving native Env trimers intact and viral infectivity unaffected. J Virol. 2011;85:5825–5839. PubMed PMC
Means RE, Desrosiers RC. Resistance of native, oligomeric envelope on simian immunodeficiency virus to digestion by glycosidases. J Virol. 2000;74:11181–11190. PubMed PMC
Raska M, Moldoveanu Z, Novak J, Hel Z, Novak L, Bozja J, Compans RW, Yang C, Mestecky J. Delivery of DNA HIV-1 vaccine to the liver induces high and long-lasting humoral immune responses. Vaccine. 2008;26:1541–1551. PubMed PMC
Li Y, Luo L, Rasool N, Kang CY. Glycosylation is necessary for the correct folding of human immunodeficiency virus gp120 in CD4 binding. J Virol. 1993;67:584–588. PubMed PMC
Doores KJ, Bonomelli C, Harvey DJ, Vasiljevic S, Dwek RA, Burton DR, Crispin M, Scanlan CN. Envelope glycans of immunodeficiency virions are almost entirely oligomannose antigens. Proc Natl Acad Sci U S A. 2010;107:13800–13805. PubMed PMC
Hemming A, Gram GJ, Bolmstedt A, Losman B, Hansen JE, Ricksten A, Olofsson S. Conserved N-linked oligosaccharides of the C-terminal portion of human immunodeficiency virus type 1 gp120 and viral susceptibility to neutralizing antibodies. Arch Virol. 1996;141:2139–2151. PubMed
Trkola A, Purtscher M, Muster T, Ballaun C, Buchacher A, Sullivan N, Srinivasan K, Sodroski J, Moore JP, Katinger H. Human monoclonal antibody 2G12 defines a distinctive neutralization epitope on the gp120 glycoprotein of human immunodeficiency virus type 1. J Virol. 1996;70:1100–1108. PubMed PMC
Doria-Rose NA, Georgiev I, O’Dell S, Chuang GY, Staupe RP, McLellan JS, Gorman J, Pancera M, Bonsignori M, Haynes BF, Burton DR, Koff WC, Kwong PD, Mascola JR. A short segment of the HIV-1 gp120 V1/V2 region is a major determinant of resistance to V1/V2 neutralizing antibodies. J Virol. 2012;86:8319–8323. PubMed PMC
Zhu J, O’Dell S, Ofek G, Pancera M, Wu X, Zhang B, Zhang Z, Mullikin JC, Simek M, Burton DR, Koff WC, Shapiro L, Mascola JR, Kwong PD. Somatic populations of PGT135-137 HIV-1-neutralizing antibodies identified by 454 pyrosequencing and bioinformatics. Front Microbiol. 2012;3:315. PubMed PMC
Huang CC, Tang M, Zhang MY, Majeed S, Montabana E, Stanfield RL, Dimitrov DS, Korber B, Sodroski J, Wilson IA, Wyatt R, Kwong PD. Structure of a V3-containing HIV-1 gp120 core. Science. 2005;310:1025–1028. PubMed PMC
Flynn NM, Forthal DN, Harro CD, Judson FN, Mayer KH, Para MF. Placebo-controlled phase 3 trial of a recombinant glycoprotein 120 vaccine to prevent HIV-1 infection. J Infect Dis. 2005;191:654–665. PubMed
Raux M, Finkielsztejn L, Salmon-Ceron D, Bouchez H, Excler JL, Dulioust E, Grouin JM, Sicard D, Blondeau C. IgG subclass distribution in serum and various mucosal fluids of HIV type 1-infected subjects. AIDS Res Hum Retroviruses. 2000;16:583–594. PubMed
Xu W, Santini PA, Sullivan JS, He B, Shan M, Ball SC, Dyer WB, Ketas TJ, Chadburn A, Cohen-Gould L, Knowles DM, Chiu A, Sanders RW, Chen K, Cerutti A. HIV-1 evades virus-specific IgG2 and IgA responses by targeting systemic and intestinal B cells via long-range intercellular conduits. Nat Immunol. 2009;10:1008–1017. PubMed PMC
Mestecky J, Wei Q, Alexander R, Raska M, Novak J, Moldoveanu Z. Humoral Immune Responses to HIV in the Mucosal Secretions and Sera of HIV-Infected Women. Am J Reprod Immunol. 2014;71:600–607. PubMed PMC
Riedner G, Hoffmann O, Rusizoka M, Mmbando D, Maboko L, Grosskurth H, Todd J, Hayes R, Hoelscher M. Decline in sexually transmitted infection prevalence and HIV incidence in female barworkers attending prevention and care services in Mbeya Region, Tanzania. Aids. 2006;20:609–615. PubMed
Hoffmann O, Zaba B, Wolff B, Sanga E, Maboko L, Mmbando D, von Sonnenburg F, Hoelscher M. Methodological lessons from a cohort study of high risk women in Tanzania. Sex Transm Infect. 2004;80(Suppl 2):ii69–ii73. PubMed PMC
Mestecky J, Wright PF, Lopalco L, Staats HF, Kozlowski PA, Moldoveanu Z, Alexander RC, Kulhavy R, Pastori C, Maboko L, Riedner G, Zhu Y, Wrinn T, Hoelscher M. Scarcity or absence of humoral immune responses in the plasma and cervicovaginal lavage fluids of heavily HIV-1-exposed but persistently seronegative women. AIDS Res Hum Retroviruses. 2011;27:469–486. PubMed PMC
Raska M, Elliott MC, Hall S, Czernekova L, Zachova K, Moldoveanu Z, Brown R, Mestecky J, Novak J. In: Centennial Retrovirus Meeting: 29 Apr-04 May 2010; Prague. Rene D, Jiri H, Skalka AM, Jan S, editor. Medimond; 2010. HIV-1 gp120 glycosylation is cell type-specific and influences reactivity with HIV-1-specific antibodies; pp. 55–59.
Alexander R, Mestecky J. Neutralizing antibodies in mucosal secretions: IgG or IgA? Curr HIV Res. 2007;5:588–593. PubMed
Li M, Gao F, Mascola JR, Stamatatos L, Polonis VR, Koutsoukos M, Voss G, Goepfert P, Gilbert P, Greene KM, Bilska M, Kothe DL, Salazar-Gonzalez JF, Wei X, Decker JM, Hahn BH, Montefiori DC. Human immunodeficiency virus type 1 env clones from acute and early subtype B infections for standardized assessments of vaccine-elicited neutralizing antibodies. J Virol. 2005;79:10108–10125. PubMed PMC
Montefiori DC. Measuring HIV neutralization in a luciferase reporter gene assay. Methods Mol Biol. 2009;485:395–405. PubMed
Ochsenbauer C, Kappes JC. New virologic reagents for neutralizing antibody assays. Curr Opin HIV AIDS. 2009;4:418–425. PubMed
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. PubMed PMC
Glycan Positioning Impacts HIV-1 Env Glycan-Shield Density, Function, and Recognition by Antibodies
Defining HIV-1 Envelope N-Glycan Microdomains through Site-Specific Heterogeneity Profiles