Anti-47 therapy targets lymphoid aggregates in the gastrointestinal tract of HIV-1–infected individuals

Mathieu Uzzan, Minami Tokuyama, Adam K. Rosenstein, Costin Tomescu, Ivo N. SahBandar, Huaibin M. Ko, Louise Leyre, Anupa Chokola, Emma Kaplan-Lewis, Gabriela Rodriguez, Akihiro Seki, Michael J. Corley, Judith Aberg, Annalena La Porte, Eun young Park, Hideki Ueno, Ioannis Oikonomou, Itai Doron, Iliyan D. Iliev, Benjamin K. ChenJennifer Lui, Timothy W. Schacker, Glaucia C. Furtado, Sergio A. Lira, Jean Frederic Colombel, Amir Horowitz, Jean K. Lim, Nicolas Chomont, Adeeb H. Rahman, Luis J. Montaner, Lishomwa C. Ndhlovu, Saurabh Mehandru

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21 Scopus citations

Abstract

Gut homing CD4+ T cells expressing the integrin 47 are early viral targets and contribute to HIV-1 pathogenesis, likely by seeding the gastrointestinal (GI) tract with HIV. Although simianized anti-47 monoclonal antibodies have shown promise in preventing or attenuating the disease course of simian immunodeficiency virus in nonhuman primate studies, the mechanisms of drug action remain elusive. We present a cohort of individuals with mild inflammatory bowel disease and concomitant HIV-1 infection receiving anti-47 treatment. By sampling the immune inductive and effector sites of the GI tract, we have discovered that anti-47 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 maintaining viral reservoirs, their attrition by anti-47 therapy has important implications for HIV-1 therapeutics and eradication efforts and defines a rational basis for the use of anti-47 therapy in HIV-1 infection.

Original languageEnglish (US)
Article numbereaau4711
JournalScience Translational Medicine
Volume10
Issue number461
DOIs
StatePublished - Oct 3 2018

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    Uzzan, M., Tokuyama, M., Rosenstein, A. K., Tomescu, C., SahBandar, I. N., Ko, H. M., Leyre, L., Chokola, A., Kaplan-Lewis, E., Rodriguez, G., Seki, A., Corley, M. J., Aberg, J., Porte, A. L., Park, E. Y., Ueno, H., Oikonomou, I., Doron, I., Iliev, I. D., ... Mehandru, S. (2018). Anti-47 therapy targets lymphoid aggregates in the gastrointestinal tract of HIV-1–infected individuals. Science Translational Medicine, 10(461), [eaau4711]. https://doi.org/10.1126/scitranslmed.aau4711