P2X Antagonists Inhibit HIV-1 Productive Infection and Inflammatory Cytokines Interleukin-10 (IL-10) and IL-1β in a Human Tonsil Explant Model

Author:

Soare Alexandra Y.1,Durham Natasha D.12,Gopal Ramya3,Tweel Benjamin4,Hoffman Kevin W.5,Brown Julia A.5,O’Brien Megan13,Bhardwaj Nina3,Lim Jean K.5,Chen Benjamin K.1,Swartz Talia H.1ORCID

Affiliation:

1. Division of Infectious Diseases, Department of Medicine, Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA

2. Division of Molecular Biology and Microbiology, Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, Massachusetts, USA

3. Division of Hematology and Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA

4. Department of Otolaryngology, Icahn School of Medicine at Mount Sinai, New York, New York, USA

5. Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA

Abstract

Patients who are chronically infected with HIV-1 experience sequelae related to chronic inflammation. The mechanisms of this inflammation have not been elucidated. Here, we describe a class of drugs that target the P2X proinflammatory signaling receptors in a human tonsil explant model. This model highlights differences in HIV-1 stimulation of lymphoid tissue inflammation and peripheral blood. These drugs serve to block both HIV-1 infection and production of IL-10 and IL-1β in lymphoid tissue, suggesting a novel approach to HIV-1 therapeutics in which both HIV-1 replication and inflammatory signaling are simultaneously targeted.

Funder

HHS | National Institutes of Health

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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