The Role of Integrin α4β7 in HIV Pathogenesis and Treatment

• Authors: James Arthos, National Institutes of Health; Claudia Cicala, National Institutes of Health; Fatima Nawaz, National Institutes of Health; Siddappa N. Byrareddy, University of Nebraska Medical Center; Francois Villinger, University of Louisiana Lafayette; Philip J. Santangelo, Georgia Institute of Technology; Aftab A Ansari, Emory University; Anthony S. Fauci, National Institutes of Health
• Journal Title: Current HIV/AIDS Reports
• Volume: Volume 15, Number 2
• Publisher: Current Medicine Group | 2018-04-01, Pages 127-135
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1007/s11904-018-0382-3
• Subjects: Health Sciences, Pathology; Health Sciences, Medicine and Surgery
• Keywords: Science & Technology; Life Sciences & Biomedicine; Infectious Diseases; HIV/SIV; GALT; Integrin alpha(4)beta(7); Inflammatory bowel disease; Mucosal transmission; Antiretroviral therapy; SIMIAN IMMUNODEFICIENCY VIRUS; CELL-ADHESION MOLECULE-1; T-CELLS; GASTROINTESTINAL-TRACT; CHLAMYDIA-TRACHOMATIS; LYMPHOID-TISSUE; ANTIRETROVIRAL THERAPY; ULCERATIVE-COLITIS; IMMUNE ACTIVATION; MUCOSAL BARRIER

Abstract

Purpose of Review: Acute HIV infection is characterized by high-level viral replication throughout the body’s lymphoid system, particularly in gut-associated lymphoid tissues resulting in damage to structural components of gut tissue. This damage is irreversible and believed to contribute to the development of immune deficiencies. Antiretroviral therapy (ART) does not restore gut structure and function. Studies in macaques point to an alternative treatment strategy that may ameliorate gut damage. Integrin α 4 β 7 mediates the homing of lymphocytes to gut tissues. Vedolizumab, a monoclonal antibody (mAb) antagonist of α 4 β 7 , has demonstrated efficacy and has been approved for the treatment of inflammatory bowel disease in humans. Here, we describe our current knowledge, and the gaps in our understanding, of the role of α 4 β 7 in HIV pathogenesis and treatment. Recent Findings: When administered to macaques prior to infection, a nonhuman primate analogue of vedolizumab prevents transmission of SIV. In combination with ART, this mAb facilitates durable virologic control following treatment interruption. Summary: Targeting α 4 β 7 represents a novel therapeutic approach to prevent and treat HIV infection.