Publication: Identification of new regions in HIV-1 gp120 Variable 2 and 3 Loops that Bind to α4β7 Integrin Receptor
Issued Date
2015-12-01
Resource Type
ISSN
19326203
Other identifier(s)
2-s2.0-84961356295
Rights
Mahidol University
Rights Holder(s)
SCOPUS
Bibliographic Citation
PLoS ONE. Vol.10, No.12 (2015)
Suggested Citation
Kristina K. Peachman, Nicos Karasavvas, Agnes Laurence Chenine, Robert McLinden, Supachai Rerks-Ngarm, Kaewkungwal Jaranit, Sorachai Nitayaphan, Punnee Pitisuttithum, Sodsai Tovanabutra, Susan Zolla-Pazner, Nelson L. Michael, Jerome H. Kim, Carl R. Alving, Mangala Rao Identification of new regions in HIV-1 gp120 Variable 2 and 3 Loops that Bind to α4β7 Integrin Receptor. PLoS ONE. Vol.10, No.12 (2015). doi:10.1371/journal.pone.0143895 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/35069
Research Projects
Organizational Units
Authors
Journal Issue
Thesis
Title
Identification of new regions in HIV-1 gp120 Variable 2 and 3 Loops that Bind to α4β7 Integrin Receptor
Other Contributor(s)
Walter Reed Army Institute of Research
Henry M. Jackson Foundation for the Advancement of Military Medicine
Armed Forces Research Institute of Medical Sciences, Thailand
Thailand Ministry of Public Health
Mahidol University
Royal Thai Army
NYU School of Medicine
Icahn School of Medicine at Mount Sinai
International Vaccine Institute, Seoul
Henry M. Jackson Foundation for the Advancement of Military Medicine
Armed Forces Research Institute of Medical Sciences, Thailand
Thailand Ministry of Public Health
Mahidol University
Royal Thai Army
NYU School of Medicine
Icahn School of Medicine at Mount Sinai
International Vaccine Institute, Seoul
Abstract
Background The gut mucosal homing integrin receptor α4β7 present on activated CD4+ T cells interacts with the HIV-1 gp120 second variable loop (V2). Case control analysis of the RV144 phase III vaccine trial demonstrated that plasma IgG binding antibodies specific to scaffolded proteins expressing the first and second variable regions (V1V2) of HIV envelope protein gp120 containing the α4β7 binding motif correlated inversely with risk of infection. Subsequently antibodies to the V3 region were also shown to correlate with protection. The integrin receptor α4β7 was shown to interact with the LDI/V motif on V2 loop but recent studies suggest that additional regions of V2 loop could interact with the α4β7. Thus, there may be several regions on the V2 and possibly V3 loops that may be involved in this binding. Using a cell line, that constitutively expressed α4β7 receptors but lacked CD4, we examined the contribution of V2 and V3 loops and the ability of V2 peptide-, V2 integrin-, V3-specific monoclonal antibodies (mAbs), and purified IgG from RV144 vaccinees to block the V2/V3-α4β7 interaction. Results We demonstrate that α4β7 on RPMI8866 cells bound specifically to its natural ligand mucosal addressin cell adhesion molecule-1 (MAdCAM-1) as well as to cyclic-V2 and cyclic-V3 peptides. This binding was inhibited by anti-α4β7-specific monoclonal antibody (mAb) ACT-1, mAbs specific to either V2 or V3 loops, and by purified primary virions or infectious molecular clones expressing envelopes from acute or chronic subtypes A, C, and CRF01-AE viruses. Plasma from HIV-1 infected Thai individuals as well as purified IgG from uninfected RV144 vaccinees inhibited (0-50%) the binding of V2 and V3 peptides to α4β7. Conclusion Our results indicate that in addition to the tripeptide LDI/V motif, other regions of the V2 and V3 loops of gp120 were involved in binding to α4β7 receptors and this interaction was blocked by anti-V2 peptide, anti-V2 integrin, and anti-V3 antibodies. The ability of purified IgG from some of the uninfected RV144 vaccinees to inhibit α4β7 raises the hypothesis that anti-V2 and anti-V3 antibodies may play a role in blocking the gp120-α4β7 interaction after vaccination and thus prevent HIV-1 acquisition.