Simone I. Richardson
Elin S. Gray, Edith Cowan University
Nonhlanhla N. Mkhize
Daniel J. Sheward
Bronwen E. Lambson
Constantinos K. Wibmer
Jo A.S Passmore
Quarraisha A. Karim
Salim S.A. Karim
Penny L. Moore
BioMed Central Ltd.
Faculty of Health, Engineering and Science
School of Medical Sciences / ECU Melanoma Research Foundation
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 (
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