The integrin α4β7 forms a complex with cell-surface CD4 and defines a T-cell subset that is highly susceptible to infection by HIV-1

Claudia Cicala, Elena Martinelli, Jonathan P. McNally, Diana J. Goode, Ravindra Gopaul, Joseph Hiatt, Katija Jelicic, Shyamasundaran Kottilil, Katilyn Macleod, Angeline O'Shea, Nikita Patel, Donald Van Ryk, Danlan Wei, Massimiliano Pascuccio, Ling Yi, Lyle McKinnon, Preson Izulla, Joshua Kimani, Rupert Kaul, Anthony S. FauciJames Arthos

Research output: Contribution to journalArticle

195 Scopus citations

Abstract

Both activated and resting CD4+ T cells in mucosal tissues play important roles in the earliest phases of infection after sexual transmission of HIV-1, a process that is inefficient. HIV-1 gp120 binds to integrin α4β7 (α4β7), the gut mucosal homing receptor. We find that α4β7high CD4+T cells are more susceptible to productive infection than are α4β7low-neg CD4+ T cells in part because this cellular subset is enriched with metabolically active CD4+ T cells. α4β7high CD4+ T cells are CCR5high and CXCR4low; on these cells, α4β7 appears in a complex with CD4. The specific affinity of gp120 for α4β7 provides a mechanism for HIV-1 to target activated cells that are critical for efficient virus propagation and dissemination following sexual transmission.

Original languageEnglish (US)
Pages (from-to)20877-20882
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number49
DOIs
StatePublished - Dec 8 2009

All Science Journal Classification (ASJC) codes

  • General

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    Cicala, C., Martinelli, E., McNally, J. P., Goode, D. J., Gopaul, R., Hiatt, J., Jelicic, K., Kottilil, S., Macleod, K., O'Shea, A., Patel, N., Van Ryk, D., Wei, D., Pascuccio, M., Yi, L., McKinnon, L., Izulla, P., Kimani, J., Kaul, R., ... Arthos, J. (2009). The integrin α4β7 forms a complex with cell-surface CD4 and defines a T-cell subset that is highly susceptible to infection by HIV-1. Proceedings of the National Academy of Sciences of the United States of America, 106(49), 20877-20882. https://doi.org/10.1073/pnas.0911796106