Targeting α4β7 integrin reduces mucosal transmission of simian immunodeficiency virus and protects gut-associated lymphoid tissue from infection

Nat Med. 2014 Dec;20(12):1397-400. doi: 10.1038/nm.3715. Epub 2014 Nov 24.

Abstract

α4β7 integrin-expressing CD4(+) T cells preferentially traffic to gut-associated lymphoid tissue (GALT) and have a key role in HIV and simian immunodeficiency virus (SIV) pathogenesis. We show here that the administration of an anti-α4β7 monoclonal antibody just prior to and during acute infection protects rhesus macaques from transmission following repeated low-dose intravaginal challenges with SIVmac251. In treated animals that became infected, the GALT was significantly protected from infection and CD4(+) T cell numbers were maintained in both the blood and the GALT. Thus, targeting α4β7 reduces mucosal transmission of SIV in macaques.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology*
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes / drug effects*
  • CD4-Positive T-Lymphocytes / immunology
  • Cervix Uteri / virology
  • Colon / virology
  • DNA, Viral / analysis*
  • Female
  • Ileum / virology
  • Integrins / antagonists & inhibitors*
  • Integrins / immunology
  • Intestinal Mucosa / drug effects*
  • Intestinal Mucosa / immunology
  • Jejunum / virology
  • Lymphoid Tissue / drug effects*
  • Lymphoid Tissue / immunology
  • Macaca mulatta
  • Mucous Membrane / drug effects
  • Mucous Membrane / immunology
  • Simian Acquired Immunodeficiency Syndrome / immunology
  • Simian Acquired Immunodeficiency Syndrome / transmission*
  • Simian Immunodeficiency Virus / genetics
  • Vagina / drug effects*
  • Vagina / immunology
  • Viral Load

Substances

  • Antibodies, Monoclonal
  • DNA, Viral
  • Integrins
  • integrin alpha4beta7