Gammaherpesvirus Usurps Host IL-17 Signaling To Support the Establishment of Chronic Infection.

Autor:	Jondle CN; Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA cjondle@mcw.edu vera@mcw.edu., Johnson KE; Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA., Aurubin C; Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA., Sylvester P; Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA., Xin G; Blood Research Institute, Versiti, Milwaukee, Wisconsin, USA., Cui W; Blood Research Institute, Versiti, Milwaukee, Wisconsin, USA., Huppler AR; Department of Pediatrics, Children's Hospital of Wisconsin Research Institute, Medical College of Wisconsin, Milwaukee, Wisconsin, USA., Tarakanova VL; Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA cjondle@mcw.edu vera@mcw.edu.; Cancer Center, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Jazyk:	angličtina
Zdroj:	MBio [mBio] 2021 Apr 06; Vol. 12 (2). Date of Electronic Publication: 2021 Apr 06.
DOI:	10.1128/mBio.00566-21
Abstrakt:	Gammaherpesviruses establish lifelong infection and are associated with a variety of cancers, including B cell lymphomas. These viruses manipulate the B cell differentiation process to establish lifelong infection in memory B cells. Specifically, gammaherpesviruses infect naive B cells and promote entry of both infected and uninfected naive B cells into germinal centers, where the virus usurps rapid proliferation of germinal center B cells to exponentially increase its cellular latent reservoir. In addition to facilitating the establishment of latent infection, germinal center B cells are thought to be the target of viral transformation. In this study, we have uncovered a novel proviral role of host interleukin 17A (IL-17A), a well-established antibacterial and antifungal factor. Loss of IL-17A signaling attenuated the establishment of chronic gammaherpesvirus infection and gammaherpesvirus-driven germinal center response in a route of inoculation-dependent manner. Further, IL-17A treatment directly supported gammaherpesvirus reactivation and de novo lytic infection. This study is the first demonstration of a multifaceted proviral role of IL-17 signaling. IMPORTANCE Gammaherpesviruses establish lifelong infections in a majority of humans and are associated with B cell lymphomas. IL-17A is a host cytokine that plays a well-established role in the clearance of bacterial and fungal infections; however, the role of IL-17A in viral infections is poorly understood. In this study, we show that IL-17A signaling promoted the establishment of chronic gammaherpesvirus infection following the mucosal route of infection, viral lytic replication, and reactivation from latency. Thus, our study unveils a novel proviral role of IL-17A signaling in gammaherpesvirus infection. (Copyright © 2021 Jondle et al.)
Databáze:	MEDLINE
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