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PMID: 19933330 Published · ppublish English Journal Article Research Support, N.I.H., Intramural

The integrin alpha4beta7 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 ·2009-12-08 ·Pages 20877-82

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

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 alpha(4)beta(7) (alpha(4)beta(7)), the gut mucosal homing receptor. We find that alpha(4)beta(7)(high) CD4(+) T cells are more susceptible to productive infection than are alpha(4)beta(7)(low-neg) CD4(+) T cells in part because this cellular subset is enriched with metabolically active CD4(+) T cells. alpha(4)beta(7)(high) CD4(+) T cells are CCR5(high) and CXCR4(low); on these cells, alpha(4)beta(7) appears in a complex with CD4. The specific affinity of gp120 for alpha(4)beta(7) provides a mechanism for HIV-1 to target activated cells that are critical for efficient virus propagation and dissemination following sexual transmission.

MeSH Terms
Antibodies, Monoclonal/pharmacology CD4 Antigens/immunology CD4-Positive T-Lymphocytes/drug effects,immunology,virology Cell Membrane/drug effects,immunology,virology Female Genitalia, Female/drug effects,immunology HIV Infections/immunology HIV-1/drug effects,immunology,physiology Humans Immunoprecipitation Integrins/immunology Intestinal Mucosa/drug effects,immunology Lymphocyte Activation/drug effects,immunology Receptors, CCR5/metabolism T-Lymphocyte Subsets/drug effects,immunology,virology Virus Replication/drug effects
Chemicals
Antibodies, Monoclonal CD4 Antigens Integrins Receptors, CCR5 integrin alpha4beta7
Authors & Affiliations
21 authors, click to expand affiliations / ORCID
Cicala Claudia
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. ccicala@niaid.nih.gov
Martinelli Elena
McNally Jonathan P
Goode Diana J
Gopaul Ravindra
Hiatt Joseph
Jelicic Katija
Kottilil Shyamasundaran
Macleod Katilyn
O'Shea Angeline
Patel Nikita
Van Ryk Donald
Wei Danlan
Pascuccio Massimiliano
Yi Ling
McKinnon Lyle
Izulla Preson
Kimani Joshua
Kaul Rupert
Fauci Anthony S
Arthos James
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
1091-6490
DOI
10.1073/pnas.0911796106
Email
ccicala@niaid.nih.gov
Published
2009-12-08
Epub
2009-00-20
Pages
20877-82
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC2780317
Subset
IM
Grants
Intramural NIH HHS · United States
External Links
PubMed source DOI: 10.1073/pnas.0911796106 PMC Full Text View journal details
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