Work

Prolonged experimental CD4+ T-cell depletion does not cause disease progression in SIV-infected African green monkeys

Year: 2023

Type: article

Abstract: CD4+ T-cell depletion is a hallmark of HIV infection, leading to impairment of cellular immunity and opportunistic infections, but its contribution to SIV/HIV-associated gut dysfunction is unknown. Chronically SIV-infected African Green Monkeys (AGMs) partially recover mucosal CD4+ T-cells, maintain gut integrity and do not progress to AIDS. Here we assess the impact of prolonged, antibody-mediated CD4 + T-cell depletion on gut integrity and natural history of SIV infection in AGMs. All circulating CD4+ T-cells and >90% of mucosal CD4+ T-cells are depleted. Plasma viral loads and cell-associated viral RNA in tissues are lower in CD4+-cell-depleted animals. CD4+-cell-depleted AGMs maintain gut integrity, control immune activation and do not progress to AIDS. We thus conclude that CD4+ T-cell depletion is not a determinant of SIV-related gut dysfunction, when gastrointestinal tract epithelial damage and inflammation are absent, suggesting that disease progression and resistance to AIDS are independent of CD4+ T-cell restoration in SIVagm-infected AGMs.

Source: Nature Communications

DOI: 10.1038/s41467-023-36379-2

Authors: Quentin Le Hingrat, Paola Sette, Cuiling Xu, Andrew R. Rahmberg, Lilas Tarnus, Haritha Annapureddy, Adam Kleinman, Egidio Brocca-Cofano, Ranjit Sivanandham, Sindhuja Sivanandham, Tianyu He, Daniel J. Capreri, Dongzhu Ma, Jacob D. Estes, Jason M. Brenchley, Cristian Apetrei, Ivona Pandrea

Institutions: University of Pittsburgh, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Oregon National Primate Research Center, Oregon Health & Science University

Language: English

Topic: HIV Research and Treatment

Subfield: Virology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $6,290

Funders: U.S. Department of Health and Human Services, National Institutes of Health, National Heart, Lung, and Blood Institute, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, NHLBI Division of Intramural Research

Awards: Impact of NETosis on SIV Pathogenesis and Response to Treatment, G127245035, G2220495165, G2676756969, G3155095577, G3155619969, G3322103365, G4146764, G4283612380, G4383402899, Mechanistic Studies of Gut Dysfunction Exacerbation due to SARS-CoV-2 in HIV/SIV infected Individuals, Myocardial Vulnerability to Ischemia-Induced Dysfunction and Heart Failure: The Impact of HIV/SIV, ART, and Targeted Immunotherapy, G5984486114, G6038722010, G6130246883, Impact of metabolic programing of T cells from the GI tract and related tissues on HIV reservoir seeding, maintenance and reactivation, G7073421420, G7369284765, G7751178727, New Strategy to Improve Gastrointestinal Health in SIV/HIV, SIV Pathogenesis in African Green Monkeys and Pigtailed Macaques, Animal Model for Testing SIV Latency Reversal Strategies, G8730238661, G9000024899, G9000130844, G9000167793, G9000243865, G9000245809, Assessing the Role of GI Tract Dysfunction to HIV/SIV Disease Progression

OpenAlex ID: W4321487705

FWCI: 1.539

Cites: 70

Cited by: 13

Related to: 10