Antiretroviral Therapy in Simian Immunodeficiency Virus-Infected Sooty Mangabeys: Implications for AIDS Pathogenesis

• Type of Material: Article
• Authors: Francesca Calascibetta, Emory University; Luca Micci, Emory University; Diane Carnathan, Emory University; Benton Lawson, Emory University; Thomas Howerton Vanderford, Emory University; Steven Bosinger, Emory University; Kirk Easley, Emory University; Ann Chahroudi, Emory University; Joseph Mackel, Emory University; Brandon F. Keele, Leidos Biomedical Research, Inc.; Samuel Long, Leidos Biomedical Research, Inc.; Jeffrey Lifson, Leidos Biomedical Research, Inc.; Mirko Paiardini, Emory University; Guido Silvestri, Emory University
• Language: English
• Date: 2016-08-01
• Publisher: American Society of Microbiology
• Publication Version: Final Published Version
• Copyright Statement: © 2016, American Society for Microbiology. All Rights Reserved.
• Final Published Version (URL): http://dx.doi.org/10.1128/JVI.00598-16
• Title of Journal or Parent Work: Journal of Virology
• Volume: 90
• Issue: 16
• Start Page: 7541
• End Page: 7551
• Grant/Funding Information: This work was supported by an R33 NIH grant (AI104278) with principal investigators Guido Silvestri and Mirko Paiardini. Research reported in this publication was also supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award number P51 OD011132 (to the YNPRC) and also in part by Merck.
• Keywords: Life Sciences & Biomedicine; Virology; HOMEOSTATIC PROLIFERATION; IMMUNE ACTIVATION; Science & Technology; CD4(+) T-CELLS; SUPPRESSION; SIV INFECTION; CHRONIC HIV-INFECTION; LENTIVIRAL INFECTIONS; RHESUS MACAQUES; DEPLETION; VIRAL RESERVOIR
• Research Categories: Biology, Virology; Health Sciences, Immunology

Abstract

Simian immunodeficiency virus (SIV)-infected sooty mangabeys (SMs) do not develop AIDS despite high levels of viremia. Key factors involved in the benign course of SIV infection in SMs are the absence of chronic immune activation and low levels of infection of CD4+ central memory (TCM) and stem cell memory (TSCM) T cells. To better understand the role of virus replication in determining the main features of SIV infection in SMs, we treated 12 SMs with a potent antiretroviral therapy (ART) regimen for 2 to 12 months. We observed that ART suppressed viremia to<60 copies/ml of plasma in 10 of 12 animals and induced a variable decrease in the level of cell-associated SIV DNA in peripheral blood (average changes of 0.9-, 1.1-, 1.5-, and 3.7-fold for CD4+ transitional memory [TTM], TCM, effector memory [TEM], and TSCM cells, respectively). ART-treated SIV-infected SMs showed (i) increased percentages of circulating CD4+ TCM cells, (ii) increased levels of CD4+ T cells in the rectal mucosa, and (iii) significant declines in the frequencies of HLA-DR+ CD8+ T cells in the blood and rectal mucosa. In addition, we observed that ART interruption resulted in rapid viral rebound in all SIV-infected SMs, indicating that the virus reservoir persists for at least a year under ART despite lower infection levels of CD4+ TCM and TSCM cells than those seen in pathogenic SIV infections of macaques. Overall, these data indicate that ART induces specific immunological changes in SIV-infected SMs, thus suggesting that virus replication affects immune function even in the context of this clinically benign infection.