RT Journal Article
SR Electronic
T1 Anti-α4β7 therapy targets lymphoid aggregates in the gastrointestinal tract of HIV-1 infected individuals
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 346684
DO 10.1101/346684
A1 Mathieu Uzzan
A1 Minami Tokuyama
A1 Adam K. Rosenstein
A1 Costin Tomescu
A1 Ivo N. SahBandar
A1 Huaibin M. Ko
A1 Louise Leyre
A1 Anupa Chokola
A1 Emma Kaplan-Lewis
A1 Gabriela Rodriguez
A1 Akihiro Seki
A1 Michael J. Corley
A1 Judith Aberg
A1 Annalena La Porte
A1 Eun-young Park
A1 Hideki Ueno
A1 Ioannis Oikonomou
A1 Itai Doron
A1 Iliyan D. Iliev
A1 Benjamin K. Chen
A1 Jennifer Lui
A1 Timothy W. Schacker
A1 Glaucia C. Furtado
A1 Sergio A. Lira
A1 Jean-Frederic Colombel
A1 Amir Horowitz
A1 Jean K. Lim
A1 Nicolas Chomont
A1 Luis J. Montaner
A1 Lishomwa C. Ndhlovu
A1 Saurabh Mehandru
YR 2018
UL http://biorxiv.org/content/early/2018/06/14/346684.abstract
AB Herein, we present the first human study of anti-α4β7 therapy in a cohort of HIV-1 infected subjects with mild inflammatory bowel disease. α4β7+ gut homing CD4+ T cells are early viral targets and contribute to HIV-1 pathogenesis, likely by seeding the gastrointestinal (GI) tract with HIV. Although, simianized anti-α4β7 monoclonal antibodies (Mab) have shown promise in preventing or attenuating the disease course of SIV in Non-Human Primate studies, the mechanisms of drug action remain elusive and the impact on HIV-1 persistence remains unanswered. By sampling the immune inductive and effector sites of the GI tract, we have discovered that anti-α4β7 therapy led to a significant and unexpected attenuation of lymphoid aggregates, most notably in the terminal ileum. Given that lymphoid aggregates serve as important sanctuary sites for establishing and maintaining viral reservoirs, their attrition by anti-α4β7 therapy has important implications for HIV-1 therapeutics and eradication efforts, and defines a rational basis for the continued evaluation of anti-α4β7 therapy in HIV-1 infection.One Sentence Summary Anti-α4β7 integrin therapy results in attrition of lymphoid aggregates within the gastrointestinal tract of HIV-1 infected individuals