Document Type
Journal Article
Publisher
BioMed Central Ltd
Faculty
Faculty of Health, Engineering and Science
School
School of Medical Sciences / ECU Melanoma Research Foundation
RAS ID
20691
Abstract
Background: The integrin aα4β7 mediates the trafficking of immune cells to the gut associated lymphoid tissue (GALT) and is an attachment factor for the HIV gp120 envelope glycoprotein. We developed a viral replication inhibition assay to more clearly evaluate the role of aα4β7 in HIV infection and the contribution of viral and host factors. Results: Replication of 60 HIV-1 subtype C viruses collected over time from 11 individuals in the CAPRISA cohort were partially inhibited by antibodies targeting aα4β7. However, dependence on aα4β7 for replication varied substantially among viral isolates from different individuals as well as over time in some individuals. Among 8 transmitted/founder (T/F) viruses, aα4β7 reactivity was highest for viruses having P/SDI/V tri-peptide binding motifs. Mutation of T/F viruses that had LDI/L motifs to P/SDI/V resulted in greater aα4β7 reactivity, whereas mutating P/SDI/V to LDI/L motifs was associated with reduced aα4β7 binding. P/SDI/V motifs were more common among South African HIV subtype C viruses (35%) compared to subtype C viruses from other regions of Africa (
Additional Information
The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
DOI
10.1186/s12977-015-0183-3
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Comments
Richardson, S. I., Gray, E. S., Mkhize, N. N., Sheward, D. J., Lambson, B. E., Wibmer, C. K., ... & Morris, L. (2015). South African HIV-1 subtype C transmitted variants with a specific V2 motif show higher dependence on α4β7 for replication. Retrovirology, 12(1), 54. Available here