similar impact of cd8+ t cell responses on early virus dynamics during siv infections of rhesus macaques and sooty mangabeys类似的cd8 + t细胞反应的影响在早期的病毒动力学siv感染的恒河猴和乌白眉猴.pdfVIP

Similar Impact of CD8+ T Cell Responses on Early Virus Dynamics during SIV Infections of Rhesus Macaques and Sooty Mangabeys 1 2 3,4 2 1 Roger D. Kouyos *, Shari N. Gordon , Silvija I. Staprans , Guido Silvestri , Roland R. Regoes 1 Institute of Integrative Biology, ETH Zurich, Zurich, Switzerland, 2 School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America, 3 Emory Vaccine Center, Atlanta, Georgia, United States of America, 4 Merck, Philadelphia, Pennsylvania, United States of America Abstract Despite comparable levels of virus replication, simian immunodeficiency viruses (SIV) infection is non-pathogenic in natural hosts, such as sooty mangabeys (SM), whereas it is pathogenic in non-natural hosts, such as rhesus macaques (RM). Comparative studies of pathogenic and non-pathogenic SIV infection can thus shed light on the role of specific factors in SIV pathogenesis. Here, we determine the impact of target-cell limitation, CD8+ T cells, and Natural Killer (NK) cells on virus replication in the early SIV infection. To this end, we fit previously published data of experimental SIV infections in SMs and RMs with mathematical models incorporating these factors and assess to what extent the inclusion of individual factors determines the quality of the fits. We find that for both rhesus macaques and sooty mangabeys, target-cell limitation alone cannot explain the control of early virus replication, whereas including CD8+ T cells into the models significantly improves the fits. By contrast, including NK cells does only significantly improve the fits in SMs. These findings have important implications for our understanding of SIV pathogenesis as they sugge