Target Cell Availability, Rather than Breast Milk Factors, Dictates Mother-to-Infant Transmission of SIV in Sooty Mangabeys and Rhesus Macaques

• Type of Material: Article
• Authors: Ann Chahroudi, Emory University; Emily Cartwright, Emory University; S Thera Lee, Emory University; Maud Mavigner, Emory University; Diane G. Carnathan, Emory University; Benton Lawson, Emory University; Paul M. Carnathan, Emory University; Tayebeh Heshempoor, Emory University; Megan K Murphy, Emory University; Tracy Meeker, Emory University; Stephanie Ehnert, Emory University; Christopher Souder, Emory University; James Else, Emory University; Joyce Cohen, Emory University; Ronald G Collman, University of Pennsylvania; Thomas Howerton Vanderford, Emory University; Sallie R Permar, Duke University; Cynthia Derdeyn, Emory University; Francois Villinger, Emory University; Guido Silvestri, Emory University
• Language: English
• Date: 2014-03
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: © 2014 Chahroudi et al.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1003958
• Title of Journal or Parent Work: PLoS Pathogens
• ISSN: 1553-7366
• Volume: 10
• Issue: 3
• Grant/Funding Information: This work was supported by National Institutes of Health Grants CFAR03 Developmental Award to AC, R37 AI66998 to GS, R01 AI78775 to FV, R01 AI58706 to CAD, RR000165/OD011132 to the Yerkes National Primate Research Center, and P30 AI050409 to the Emory Center for AIDS Research.
• Research Categories: Biology, Virology; Health Sciences, Pathology

Abstract

Mother-to-infant transmission (MTIT) of HIV is a serious global health concern, with over 300,000 children newly infected in 2011. SIV infection of rhesus macaques (RMs) results in similar rates of MTIT to that of HIV in humans. In contrast, SIV infection of sooty mangabeys (SMs) rarely results in MTIT. The mechanisms underlying protection from MTIT in SMs are unknown. In this study we tested the hypotheses that breast milk factors and/or target cell availability dictate the rate of MTIT in RMs (transmitters) and SMs (non-transmitters). We measured viral loads (cell-free and cell-associated), levels of immune mediators, and the ability to inhibit SIV infection in vitro in milk obtained from lactating RMs and SMs. In addition, we assessed the levels of target cells (CD4+CCR5+ T cells) in gastrointestinal and lymphoid tissues, including those relevant to breastfeeding transmission, as well as peripheral blood from uninfected RM and SM infants. We found that frequently-transmitting RMs did not have higher levels of cell-free or cell-associated viral loads in milk compared to rarely-transmitting SMs. Milk from both RMs and SMs moderately inhibited in vitro SIV infection, and presence of the examined immune mediators in these two species did not readily explain the differential rates of transmission. Importantly, we found that the percentage of CD4+CCR5+ T cells was significantly lower in all tissues in infant SMs as compared to infant RMs despite robust levels of CD4+ T cell proliferation in both species. The difference between the frequently-transmitting RMs and rarely-transmitting SMs was most pronounced in CD4+ memory T cells in the spleen, jejunum, and colon as well as in central and effector memory CD4+ T cells in the peripheral blood. We propose that limited availability of SIV target cells in infant SMs represents a key evolutionary adaptation to reduce the risk of MTIT in SIV-infected SMs.