Functional Dynamics of the Interaction between HIV gp120 and α4β7

AIDS Research and Human RetrovirusesVol. 30, No. S1 Mucosal Target and Effector CellsFree AccessFunctional Dynamics of the Interaction between HIV gp120 and α4β7Fatima Nawaz, Claudia Cicala, Katija Jelicic, Raffaello Cimbro, Donald Van Ryk, Jocelyn Ray, Joseph Hiatt, Catherine Schwing, Danlan Wei, Massimiliano Pascuccio, Aftab A. Ansari, Anthony S. Fauci, and James ArthosFatima NawazNIAID, National Institutes of Health, Bethesda, MD, United StatesSearch for more papers by this author, Claudia CicalaNIAID, National Institutes of Health, Bethesda, MD, United StatesSearch for more papers by this author, Katija JelicicNIAID, National Institutes of Health, Bethesda, MD, United StatesSearch for more papers by this author, Raffaello CimbroJohns Hopkins University School of Medicine, Baltimore, MD, United StatesSearch for more papers by this author, Donald Van RykNIAID, National Institutes of Health, Bethesda, MD, United StatesSearch for more papers by this author, Jocelyn RayNIAID, National Institutes of Health, Bethesda, MD, United StatesSearch for more papers by this author, Joseph HiattNIAID, National Institutes of Health, Bethesda, MD, United StatesSearch for more papers by this author, Catherine SchwingNIAID, National Institutes of Health, Bethesda, MD, United StatesSearch for more papers by this author, Danlan WeiNIAID, National Institutes of Health, Bethesda, MD, United StatesSearch for more papers by this author, Massimiliano PascuccioNIAID, National Institutes of Health, Bethesda, MD, United StatesSearch for more papers by this author, Aftab A. AnsariEmory University School of Medicine, Atlanta, MD, United StatesSearch for more papers by this author, Anthony S. FauciNIAID, National Institutes of Health, Bethesda, MD, United StatesSearch for more papers by this author, and James ArthosNIAID, National Institutes of Health, Bethesda, MD, United StatesSearch for more papers by this authorPublished Online:30 Oct 2014https://doi.org/10.1089/aid.2014.5079.abstractAboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail OA17.02Background: Many isolates of HIV and SIV exhibit a specific affinity for integrin α4β7, the gut homing receptor. CD4+ T cells expressing α4β7 represent an ideal target for productive infection during mucosal transmission. However, many details surrounding the interaction between HIV and α4β7 remain unresolved. We hypothesize that the evolution of a specific interaction between HIV and α4β7 provides the virus a means to increase the efficiency of infection in mucosal tissues. Disrupting this interaction may provide a strategy to reduce or prevent mucosal transmission. Here we identify key features of the α4β7-HIV gp120 interaction that facilitate viral replication.Methods: We evaluated the capacity of gp120, by binding to α4β7, to induce cellular proliferation of primary CD4+ T cells using CFSE proliferation assays. We also examined the manner in which α4β7 is physically linked to CD4 using high-resolution confocal microscopy and fluorescence resonance energy transfer (FRET) on primary CD4+ T cells.Results: We find that CD4 and α4β7 are closely associated (<10nM) on the surface of CD4+ T cells. Both gp120 and soluble MAdCAM mediated costimulation of cellular proliferation in an α4β7-dependent manner.Conclusions: Although α4β7 is not an entry receptor we find that it is closely associated with CD4 on the cell membrane. This association suggests that α4β7 plays a role in T cell proliferation. We determined that both gp120 and MAdCAM costimulate CD4+ T cells and facilitate cellular proliferation and viral replication. We hypothesize that one of the selective pressures leading to a specific interaction between gp120 and α4β7 involves the capacity of α4β7 to promote metabolic activity that is conducive to viral replication. In the context of mucosal transmission, that is generally inefficient, these features of HIV interactions with α4β7-provide a means to increase transmission efficiency. Future studies will address the potential of targeting this interaction as a means of interfering with transmission.FiguresReferencesRelatedDetails Volume 30Issue S1Oct 2014 InformationCopyright 2014, Mary Ann Liebert, Inc.To cite this article:Fatima Nawaz, Claudia Cicala, Katija Jelicic, Raffaello Cimbro, Donald Van Ryk, Jocelyn Ray, Joseph Hiatt, Catherine Schwing, Danlan Wei, Massimiliano Pascuccio, Aftab A. Ansari, Anthony S. Fauci, and James Arthos.Functional Dynamics of the Interaction between HIV gp120 and α4β7.AIDS Research and Human Retroviruses.Oct 2014.A46-A47.http://doi.org/10.1089/aid.2014.5079.abstractPublished in Volume: 30 Issue S1: October 30, 2014PDF download