ArticlePloS one2014
Cryptic determinant of α4β7 binding in the V2 loop of HIV-1 gp120.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 35 citations in OpenAlex.
- Identification of New Regions in HIV-1 gp120 Variable 2 and 3 Loops that Bind to α4β7 Integrin Receptor.PloS one · 2015Trial
- Preferential engagement of the anti-inflammatory ATP/adenosine axis by HIV vaccine candidate with V1-deleted envelope in male rhesus macaques.Cell reports. Medicine · 2026Article
- Mosaic HIV-1 vaccine and SHIV challenge strain V2 loop sequence identity and protection in primates.NPJ vaccines · 2024Article
- The V2 domain of HIV gp120 mimics an interaction between CD4 and integrin ⍺4β7.PLoS pathogens · 2023Article
- Cholera toxin B scaffolded, focused SIV V2 epitope elicits antibodies that influence the risk of SIVFrontiers in immunology · 2023Article
- A clade C HIV-1 vaccine protects against heterologous SHIV infection by modulating IgG glycosylation and T helper response in macaques.Science immunology · 2022Article
- Structure-guided changes at the V2 apex of HIV-1 clade C trimer enhance elicitation of autologous neutralizing and broad V1V2-scaffold antibodies.Cell reports · 2022Article
- V2 hotspot optimized MVA vaccine expressing stabilized HIV-1 Clade C envelope Gp140 delays acquisition of heterologous Clade C Tier 2 challenges in Mamu-A*01 negative Rhesus Macaques.Frontiers in immunology · 2022Article
- Anti-V2 antibodies virus vulnerability revealed by envelope V1 deletion in HIV vaccine candidates.iScience · 2021Article
- Structure and Fc-Effector Function of Rhesusized Variants of Human Anti-HIV-1 IgG1s.Frontiers in immunology · 2021Article
- Article
- Unbiased Identification of Immunogenic Staphylococcus aureus Leukotoxin B-Cell Epitopes.Infection and immunity · 2020Article
- HIV-1 Vaccine Sequences Impact V1V2 Antibody Responses: A Comparison of Two Poxvirus Prime gp120 Boost Vaccine Regimens.Scientific reports · 2020Article
- HIV vaccine delayed boosting increases Env variable region 2-specific antibody effector functions.JCI insight · 2020Article
- Article
- Blocking αScience (New York, N.Y.) · 2019Article
- V2-Specific Antibodies in HIV-1 Vaccine Research and Natural Infection: Controllers or Surrogate Markers.Vaccines · 2019Review
- Common helical V1V2 conformations of HIV-1 Envelope expose the α4β7 binding site on intact virions.Nature communications · 2018Article
- Select gp120 V2 domain specific antibodies derived from HIV and SIV infection and vaccination inhibit gp120 binding to α4β7.PLoS pathogens · 2018Article
- The Role of Integrin αCurrent HIV/AIDS reports · 2018Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
The peptide segment of the second variable loop of HIV-1 spanning positions 166-181 harbors two functionally important sites. The first, spanning positions 179-181, engages the human α4β7 integrin receptor which is involved in T-cell gut-homing and may play a role in human immunodeficiency virus (HIV)-host cell interactions. The second, at positions 166-178, is a major target of anti-V2 antibodies elicited by the ALVAC/AIDSVAX vaccine used in the RV144 clinical trial. Notably, these two sites are directly adjacent, but do not overlap. Here, we report the identity of a second determinant of α4β7 binding located at positions 170-172 of the V2 loop. This segment - tripeptide QRV170-172- is located within the second site, yet functionally affects the first site. The absence of this segment abrogates α4β7 binding in peptides bearing the same sequence from position 173-185 as the V2 loops of the RV144 vaccines. However, peptides exhibiting V2 loop sequences from heterologous HIV-1 strains that include this QRV170-172 motif bind the α4β7 receptor on cells. Therefore, the peptide segment at positions 166-178 of the V2 loop of HIV-1 viruses appears to harbor a cryptic determinant of α4β7 binding. Prior studies show that the anti-V2 antibody response elicited by the RV144 vaccine, along with immune pressure inferred from a sieve analysis, is directed to this same region of the V2 loop. Accordingly, the anti-V2 antibodies that apparently reduced the risk of infection in the RV144 trial may have functioned by blocking α4β7-mediated HIV-host cell interactions via this cryptic determinant.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.