Faculty Collaboration Database

Gammaherpesvirus Usurps Host IL-17 Signaling To Support the Establishment of Chronic Infection. mBio 2021 Apr 06;12(2)

Date

04/08/2021

Pubmed ID

33824206

Pubmed Central ID

PMC8092251

DOI

10.1128/mBio.00566-21

Scopus ID

2-s2.0-85103513895 (requires institutional sign-in at Scopus site)   8 Citations

Abstract

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.

Author List

Jondle CN, Johnson KE, Aurubin C, Sylvester P, Xin G, Cui W, Huppler AR, Tarakanova VL

Authors

Anna H. Huppler MD Associate Professor in the Pediatrics department at Medical College of Wisconsin
Vera Tarakanova PhD Professor in the Microbiology and Immunology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Cells, Cultured
Chronic Disease
Female
Gammaherpesvirinae
Herpesviridae Infections
Host-Pathogen Interactions
Interleukin-17
Macrophages
Male
Mice
Mice, Inbred C57BL
Signal Transduction