Delineation and Modulation of the Natural Killer Cell Transcriptome in Rhesus Macaques During ZIKV and SIV Infections.
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2020-01
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Natural killer (NK) cells are crucial regulators of antiviral and anti-tumor immune responses. Although in humans some NK cell transcriptional programs are relatively well-established, NK cell transcriptional networks in non-human primates (NHP) remain poorly delineated. Here we performed RNA-Seq experiments using purified NK cells from experimentally naïve rhesus macaques, providing the first transcriptional characterization of pure NK cells in any NHP species. This novel NK cell transcriptomic signature (NK RMtsig) overlaps with published human NK signatures, allowing us to identify new key signaling and transcription factor networks underlying NK cell function. Finally, we show that applying NK RMtsig to an unrelated rhesus macaque cohort infected with SIVmac251 or ZIKV can sensitively detect NK cell repertoire perturbations, thus confirming applicability of this approach. In sum, we propose this NHP NK cell signature will serve as a useful resource for future studies involving infection, disease or treatment modalities in NHP.
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Aid, Malika, Daniel R Ram, Steven E Bosinger, Dan H Barouch and R Keith Reeves (2020). Delineation and Modulation of the Natural Killer Cell Transcriptome in Rhesus Macaques During ZIKV and SIV Infections. Frontiers in cellular and infection microbiology, 10. p. 194. 10.3389/fcimb.2020.00194 Retrieved from https://hdl.handle.net/10161/27268.
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Roger Keith Reeves
Dr. Reeves obtained his Ph.D. at the University of Alabama-Birmingham studying dendritic cell biology in lentivirus infections, then completed his postdoctoral training in lentivirus vaccinology, natural killer cells, and innate immunity at the New England Primate Research Center, Massachusetts General Hospital, and Harvard Medical School (HMS). He later became faculty at HMS and Beth Israel Deaconess Medical Center through the rank of Associate Professor. Upon being recruited to Duke University in 2021, Dr. Reeves became a tenured Professor in the Department of Surgery and the Department of Pathology and Director in the Duke Center for Human Systems Immunology. He currently serves as Editor-in-Chief of the journal AIDS Research and Human Retroviruses and is the immediate past chair of the NIH HIV Immunopathogenesis and Vaccine Development study section. Dr. Reeves also previously sat on NIH F13 fellowship study sections, has served on the HVTN ESI Advisory board for over a decade, and currently is Director of the Duke Center for AIDS Research Developmental Core, collectively mentoring dozens of trainees at all levels. Dr. Reeves’ research has been continuously supported by NIH for well over 15 years, having served as PI on multiple R and P grants in addition to participating in consortia grants such as the HIV Vaccine Trials Network and BEAT-HIV Delaney Cure Collaboratory. Considered a global expert in natural killer cell biology, his research has provided some of the most detailed characterizations of NK cell responses against viruses, and his team was the first to identify memory and memory-like NK cells in humans and nonhuman primates. With over 100 publications in the field and over 60 as senior author, Dr. Reeves’ group continues to focus on cutting-edge approaches to harness NK cells in the context of vaccines and immunotherapeutics for HIV, CMV, HCV, influenza, SARS-CoV-2, congenital CMV, and cancer.
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