Simian Immunodeficiency Virus Persistence in Cellular and Anatomic Reservoirs in Antiretroviral Therapy-Suppressed Infant Rhesus Macaques

Author:

Mavigner Maud1ORCID,Habib Jakob1,Deleage Claire2,Rosen Elias3,Mattingly Cameron1,Bricker Katherine1,Kashuba Angela3,Amblard Franck1,Schinazi Raymond F.1,Lawson Benton4,Vanderford Thomas H.4,Jean Sherrie4,Cohen Joyce4,McGary Colleen4,Paiardini Mirko4,Wood Matthew P.5,Sodora Donald L.5,Silvestri Guido4,Estes Jacob26,Chahroudi Ann147

Affiliation:

1. Department of Pediatrics and Center for AIDS Research, Emory University School of Medicine, Atlanta, Georgia, USA

2. AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, Maryland, USA

3. Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina, USA

4. Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA

5. Center for Infectious Disease Research, Seattle, Washington, USA

6. Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, Oregon, USA

7. Emory+Children's Center for Childhood Infections and Vaccines, Atlanta, Georgia, USA

Abstract

While antiretroviral therapy (ART) can reduce HIV replication, the virus cannot be eradicated from an infected individual, and our incomplete understanding of HIV persistence in reservoirs greatly complicates the generation of a cure for HIV infection. Given the immaturity of the infant immune system, it is critically important to study HIV reservoirs specifically in this population. Here, we established a pediatric animal model to simulate breastfeeding transmission and study SIV reservoirs in rhesus macaque (RM) infants. Our study demonstrates that ART can be safely administered to infant RMs for prolonged periods and that it efficiently controls viral replication in this model. SIV persistence was shown in blood and tissues, with similar anatomic distributions of SIV reservoirs in infant and adult RMs. However, in the peripheral blood and lymph nodes, a greater contribution of the naive CD4 + T cells to the SIV reservoir was observed in infants than in adults.

Funder

Emory + Children's Pediatric center

Campbell Family Foundation

DH | National Institute for Health Research

HHS | National Institutes of Health

Yerkes National Primate Research Center

Emory Center for AIDS Research

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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