association of activating kir copy number variation of nk cells with containment of siv replication in rhesus monkeys协会的激活吉珥拷贝数变异的nk细胞控制在恒河猴猴免疫缺陷病毒复制.pdf

Association of Activating KIR Copy Number Variation of NK Cells with Containment of SIV Replication in Rhesus Monkeys 1 1 2 1 Ina Hellmann , So-Yon Lim , Rebecca S. Gelman , Norman L. Letvin * 1 Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America, 2 Department of Biostatistics, Dana Farber Cancer Institute and Harvard School of Public Health, Boston, Massachusetts, United States of America Abstract While the contribution of CD8+ cytotoxic T lymphocytes to early containment of HIV-1 spread is well established, a role for NK cells in controlling HIV-1 replication during primary infection has been uncertain. The highly polymorphic family of KIR molecules expressed on NK cells can inhibit or activate these effector cells and might therefore modulate their activity against HIV-1-infected cells. In the present study, we investigated copy number variation in KIR3DH loci encoding the only activating KIR receptor family in rhesus monkeys and its effect on simian immunodeficiency virus (SIV) replication during primary infection in rhesus monkeys. We observed an association between copy numbers of KIR3DH genes and control of SIV replication in Mamu-A*01– rhesus monkeys that express restrictive TRIM5 alleles. These findings provide further evidence for an association between NK cells and the early containment of SIV replication, and underscore the potential importance of activating KIRs in stimulating NK cell responses to control SIV spread. Citation: Hellmann I, Lim S-Y, Gelman RS, Letvin NL (2011) Association of Activating KIR Copy Number Variation of NK Cells with Containment of SIV Replication in Rhesus Monkeys. PLoS Pathog 7(12)