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Title: Cryptic determinant of a4b7 binding in the v2 loop of hiv-1 gp120
Authors: Boonrat Tassaneetrithep
Doreen Tivon
James Swetnam
Nicos Karasavvas
Nelson L. Michael
Jerome H. Kim
Mary Marovich
Timothy Cardozo
Mahidol University
Walter Reed Army Institute of Research
NYU School of Medicine
Armed Forces Research Institute of Medical Sciences, Thailand
Google LLC
Keywords: Agricultural and Biological Sciences;Biochemistry, Genetics and Molecular Biology;Medicine
Issue Date: 29-Sep-2014
Citation: PLoS ONE. Vol.9, No.9 (2014)
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 α4b7 integrin receptor which is involved in T-cell guthoming 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 α4b7 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 α4b7 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 α4b7 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 α4b7 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 α4b7-mediated HIV-host cell interactions via this cryptic determinant.
ISSN: 19326203
Appears in Collections:Scopus 2011-2015

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