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. Fauci; James Arthos

doi:10.1073/pnas.0911796106

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

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

241 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 α4β7^high CD4⁺T cells are more susceptible to productive infection than are α4β7^low-neg CD4⁺ T cells in part because this cellular subset is enriched with metabolically active CD4⁺ T cells. α4β7^high CD4⁺ T cells are CCR5^high and CXCR4^low; 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 language	English (US)
Pages (from-to)	20877-20882
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	106
Issue number	49
DOIs	https://doi.org/10.1073/pnas.0911796106
State	Published - Dec 8 2009
Externally published	Yes

Keywords

Gut-associated lymphoid tissues (GALT)
Integrin receptor
Transmission

ASJC Scopus subject areas

General

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1073/pnas.0911796106

Cite this

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

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title = "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",

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.",

keywords = "Gut-associated lymphoid tissues (GALT), Integrin receptor, Transmission",

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

year = "2009",

month = dec,

day = "8",

doi = "10.1073/pnas.0911796106",

language = "English (US)",

volume = "106",

pages = "20877--20882",

journal = "Proceedings of the National Academy of Sciences of the United States of America",

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Cicala, C, Martinelli, E, McNally, JP, Goode, DJ, 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, Fauci, AS & 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, vol. 106, no. 49, pp. 20877-20882. https://doi.org/10.1073/pnas.0911796106

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. / Cicala, Claudia; Martinelli, Elena; McNally, Jonathan P. et al.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 106, No. 49, 08.12.2009, p. 20877-20882.

Research output: Contribution to journal › Article › peer-review

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T1 - 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

AU - Cicala, Claudia

AU - Martinelli, Elena

AU - McNally, Jonathan P.

AU - Goode, Diana J.

AU - Gopaul, Ravindra

AU - Hiatt, Joseph

AU - Jelicic, Katija

AU - Kottilil, Shyamasundaran

AU - Macleod, Katilyn

AU - O'Shea, Angeline

AU - Patel, Nikita

AU - Van Ryk, Donald

AU - Wei, Danlan

AU - Pascuccio, Massimiliano

AU - Yi, Ling

AU - McKinnon, Lyle

AU - Izulla, Preson

AU - Kimani, Joshua

AU - Kaul, Rupert

AU - Fauci, Anthony S.

AU - Arthos, James

PY - 2009/12/8

Y1 - 2009/12/8

N2 - 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.

AB - 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.

KW - Gut-associated lymphoid tissues (GALT)

KW - Integrin receptor

KW - Transmission

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