AUTHOR=Holay Namit , Kennedy Barry E. , Murphy J. Patrick , Konda Prathyusha , Giacomantonio Michael , Brauer-Chapin Tatjana , Paulo Joao A. , Kumar Vishnupriyan , Kim Youra , Elaghil Mariam , Sisson Gary , Clements Derek , Richardson Christopher , Gygi Steven P. , Gujar Shashi TITLE=After virus exposure, early bystander naïve CD8 T cell activation relies on NAD+ salvage metabolism JOURNAL=Frontiers in Immunology VOLUME=13 YEAR=2023 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.1047661 DOI=10.3389/fimmu.2022.1047661 ISSN=1664-3224 ABSTRACT=

CD8 T cells play a central role in antiviral immunity. Type I interferons are among the earliest responders after virus exposure and can cause extensive reprogramming and antigen-independent bystander activation of CD8 T cells. Although bystander activation of pre-existing memory CD8 T cells is known to play an important role in host defense and immunopathology, its impact on naïve CD8 T cells remains underappreciated. Here we report that exposure to reovirus, both in vitro or in vivo, promotes bystander activation of naïve CD8 T cells within 24 hours and that this distinct subtype of CD8 T cell displays an innate, antiviral, type I interferon sensitized signature. The induction of bystander naïve CD8 T cells is STAT1 dependent and regulated through nicotinamide phosphoribosyl transferase (NAMPT)-mediated enzymatic actions within NAD+ salvage metabolic biosynthesis. These findings identify a novel aspect of CD8 T cell activation following virus infection with implications for human health and physiology.