Evolution of antibody landscape and viral envelope escape in an HIV-1 CRF02_AG infected patient with 4E10-like antibodies
- PMID: 20003438
- PMCID: PMC2801487
- DOI: 10.1186/1742-4690-6-113
Evolution of antibody landscape and viral envelope escape in an HIV-1 CRF02_AG infected patient with 4E10-like antibodies
Abstract
Background: A minority of HIV-1 infected individuals develop broad cross-neutralizing (BCN) plasma antibodies that are capable of neutralizing a spectrum of virus variants belonging to different HIV-1 clades. The aim of this study was to identify the targeted epitopes of an individual with BCN plasma antibodies, referred to as ITM4, using peptide phage display. This study also aimed to use the selected mimotopes as tools to unravel the evolution of the antibody landscape and the viral envelope escape which may provide us with new insights for vaccine design.
Results: This study led us to identify ITM4 plasma antibodies directed to the 4E10 epitope located in the gp41 membrane-proximal external region (MPER). Analysis of antibody specificities revealed unusual immunogenic properties of the ITM4 viral envelope, as not only the V3 loop and the gp41 MPER but also the C1 and lentivirus lytic peptide 2 (LLP2) region seem to be targets of the immune system. The 4E10-like antibodies are consistently elicited during the 6-year follow up period. HIV-1 ITM4 pseudoviruses showed an increasing resistance over time to MPER monoclonal antibodies 4E10 and 2F5, although no changes are found in the critical positions of the epitope. Neutralization of COT6.15 (subtype C; 4E10-sensitive) pseudoviruses with alanine substitutions in the MPER region indicated an overlapping specificity of the 4E10 monoclonal antibody and the ITM4 follow up plasma. Moreover the 4E10-like antibodies of ITM4 contribute to the BCN capacity of the plasma.
Conclusions: Using ITM4 BCN plasma and peptide phage display technology, we have identified a patient with 4E10-like BCN antibodies. Our results indicate that the elicited 4E10-like antibodies play a role in virus neutralization. The viral RNA was isolated at different time points and the ITM4 envelope sequence analysis of both early (4E10-sensitive) and late (4E10-resistant) viruses suggest that other regions in the envelope, outside the MPER region, contribute to the accessibility and sensitivity of the 4E10 epitope. Including ITM4 specific HIV-1 Env properties in vaccine strategies may be a promising approach.
Figures





Similar articles
-
Conformational Epitope-Specific Broadly Neutralizing Plasma Antibodies Obtained from an HIV-1 Clade C-Infected Elite Neutralizer Mediate Autologous Virus Escape through Mutations in the V1 Loop.J Virol. 2016 Jan 13;90(7):3446-57. doi: 10.1128/JVI.03090-15. J Virol. 2016. PMID: 26763999 Free PMC article.
-
Selection and immune recognition of HIV-1 MPER mimotopes.Virology. 2020 Nov;550:99-108. doi: 10.1016/j.virol.2020.06.016. Epub 2020 Sep 19. Virology. 2020. PMID: 32980676
-
Anti-human immunodeficiency virus type 1 (HIV-1) antibodies 2F5 and 4E10 require surprisingly few crucial residues in the membrane-proximal external region of glycoprotein gp41 to neutralize HIV-1.J Virol. 2005 Jan;79(2):1252-61. doi: 10.1128/JVI.79.2.1252-1261.2005. J Virol. 2005. PMID: 15613352 Free PMC article.
-
Immunising with the transmembrane envelope proteins of different retroviruses including HIV-1: a comparative study.Hum Vaccin Immunother. 2013 Mar;9(3):462-70. doi: 10.4161/hv.23221. Epub 2012 Dec 18. Hum Vaccin Immunother. 2013. PMID: 23249763 Free PMC article. Review.
-
Neutralizing antibodies and control of HIV: moves and countermoves.Curr HIV/AIDS Rep. 2012 Mar;9(1):64-72. doi: 10.1007/s11904-011-0105-5. Curr HIV/AIDS Rep. 2012. PMID: 22203469 Review.
Cited by
-
Phages and HIV-1: from display to interplay.Int J Mol Sci. 2012;13(4):4727-4794. doi: 10.3390/ijms13044727. Epub 2012 Apr 13. Int J Mol Sci. 2012. PMID: 22606007 Free PMC article. Review.
-
Rational design of HIV vaccine and microbicides: report of the EUROPRISE annual conference.J Transl Med. 2010 Jul 26;8:72. doi: 10.1186/1479-5876-8-72. J Transl Med. 2010. PMID: 20659333 Free PMC article.
-
The genetic bottleneck in vertical transmission of subtype C HIV-1 is not driven by selection of especially neutralization-resistant virus from the maternal viral population.J Virol. 2011 Aug;85(16):8253-62. doi: 10.1128/JVI.00197-11. Epub 2011 May 18. J Virol. 2011. PMID: 21593171 Free PMC article.
References
-
- Nyambi PN, Lewi P, Peeters M, Janssens W, Heyndrickx L, Fransen K, Andries K, Haesevelde M Vanden, Heeney J, Piot P, Groen G van der. Study of the dynamics of neutralization escape mutants in a chimpanzee naturally infected with the simian immunodeficiency virus SIVcpz-ant. J Virol. 1997;71:2320–2330. - PMC - PubMed
-
- Binley JM, Wrin T, Korber B, Zwick MB, Wang M, Chappey C, Stiegler G, Kunert R, Zolla-Pazner S, Katinger H, Petropoulos CJ, Burton DR. Comprehensive cross-clade neutralization analysis of a panel of anti-human immunodeficiency virus type 1 monoclonal antibodies. J Virol. 2004;78:13232–13252. doi: 10.1128/JVI.78.23.13232-13252.2004. - DOI - PMC - PubMed
-
- Ferrantelli F, Rasmussen RA, Buckley KA, Li PL, Wang T, Montefiori DC, Katinger H, Stiegler G, Anderson DC, McClure HM, Ruprecht RM. Complete protection of neonatal rhesus macaques against oral exposure to pathogenic simian-human immunodeficiency virus by human anti-HIV monoclonal antibodies. J Infect Dis. 2004;189:2167–2173. doi: 10.1086/420833. - DOI - PubMed
Publication types
MeSH terms
Substances
Associated data
- Actions
- Actions
- Actions
- Actions
LinkOut - more resources
Full Text Sources
Medical