Simian-Human Immunodeficiency Virus SHIV.C.CH505 Persistence in ART-Suppressed Infant Macaques Is Characterized by Elevated SHIV RNA in the Gut and a High Abundance of Intact SHIV DNA in Naive CD4 <sup>+</sup> T Cells
Veronica Obregon-Perko, Katherine M. Bricker, Gloria Mensah, Ferzan Uddin, Mithra R. Kumar, Emily J. Fray, Robert F. Siliciano, Nils Schoof, Anna M. Horner, Maud Mavigner, Shan Liang, Thomas H. Vanderford, Julian Sass, Cliburn Chan, Stella J. Berendam, Katharine J. Bar, George M. Shaw, Guido Silvestri, Genevieve G. Fouda, Sallie R. Permar, Ann Chahroudi
Abstract
Uncovering the sanctuaries of the long-lived HIV-1 reservoir is crucial to develop cure strategies. Pediatric immunity is distinct from that of adults, which may alter where the reservoir is established in infancy. Thus, it is important to utilize pediatric models to inform cure-directed approaches for HIV-1-infected children. We used an infant rhesus macaque model of HIV-1 infection via breastfeeding to identify key sites of viral persistence under antiretroviral therapy (ART). The gastrointestinal tract was found to be a site for low-level viral transcription during ART. We also show that naive CD4 + T cells harbored intact provirus and were a major contributor to blood and lymphoid reservoir size. This is particularly striking, as memory CD4 + T cells are generally regarded as the main source of latent HIV/simian immunodeficiency virus (SIV) infection of adult humans and rhesus macaques. Our findings highlight unique features of reservoir composition in pediatric infection that should be considered for eradication efforts.