期刊
RETROVIROLOGY
卷 12, 期 -, 页码 -出版社
BMC
DOI: 10.1186/s12977-015-0183-3
关键词
HIV entry; alpha 4 beta 7; Tripeptide-binding motif; Bacterial vaginosis; Cytokines
类别
资金
- K-RITH
- PRF
- NRF
- National Institute of Allergy and Infectious Diseases (NIAID)
- National Institutes for Health (NIH)
- U.S. Department of Health and Human Services [AI51794]
- [089933/Z/09/Z]
Background: The integrin alpha 4 beta 7 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 alpha 4 beta 7 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 alpha 4 beta 7. However, dependence on alpha 4 beta 7 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, alpha 4 beta 7 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 alpha 4 beta 7 reactivity, whereas mutating P/SDI/V to LDI/L motifs was associated with reduced alpha 4 beta 7 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 (<8%) and to other subtypes, due in part to a founder effect. In addition, individuals with bacterial vaginosis (BV) and who had higher concentrations of IL-7, IL-8 and IL-1 alpha in the genital tract had T/F viruses with higher alpha 4 beta 7 dependence for replication, suggesting that viruses with P/SDI/V motifs may be preferentially transmitted in the presence of BV in this population. Conclusions: Collectively, these data suggest a role for alpha 4 beta 7 in HIV infection that is influenced by both viral and host factors including the sequence of the alpha 4 beta 7 binding motif, the cytokine milieu and BV in the genital tract. The higher frequency of P/SDI/V sequences among South African HIV-1 subtype C viruses may have particular significance for the role of alpha 4 beta 7 in this geographical region.
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