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.

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.

• Authors: 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
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 106 Issue 49 Pg. 20877-82 (Dec 08 2009) ISSN: 1091-6490 [Electronic] United States
• PMID: 19933330 (Publication Type: Journal Article, Research Support, N.I.H., Intramural)

Chemical References

• Antibodies, Monoclonal
• CD4 Antigens
• Integrins
• Receptors, CCR5
• integrin alpha4beta7

Topics

• 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)