Kaposi’s Sarcoma-Associated Herpesvirus Reduces Cellular Myeloid Differentiation Primary-Response Gene 88 (MyD88) Expression via Modulation of Its RNA

Authors

Amy Lingel, University of Nebraska-LincolnFollow
Erica Ehlers, University of Nebraska-Lincoln
Qianli Wang, University of Nebraska-Lincoln
Mingxia Cao, University of Nebraska-Lincoln
Charles Wood, University of Nebraska-LincolnFollow
Rongtuan Lin, McGill University
Luwen Zhang, University of Nebraska-LincolnFollow

Document Type

Article

Date of this Version

2016

Citation

Journal of Virology January 2016 Volume 90 Number 1

Comments

Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Abstract

Kaposi’s sarcoma (KS)-associated herpesvirus (KSHV) is a human gammaherpesvirus associated with several human malignancies. The replication and transcription activator (RTA) is necessary and sufficient for the switch from KSHV latency to lytic replication. Interleukin 1 (IL-1) is a major mediator for inflammation and plays an important role in both innate and adaptive immunity. Myeloid differentiation primary response gene 88 (MyD88) is an essential adaptor molecule for IL-1 as well as most Toll-like receptor signaling. In this study, we identified a novel mechanism by which KSHV interferes with host inflammation and immunity. KSHV RTA specifically reduces the steady-state protein levels of MyD88, and physiological levels of MyD88 are downregulated during KSHV lytic replication when RTA is expressed. The N-terminal region of RTA is required for the reduction of MyD88. Additional studies demonstrated that RTA targets MyD88 expression at the RNA level, inhibits RNA synthesis of MyD88, and may bind MyD88 RNA. Finally, RTA inhibits IL-1-mediated activation of NF-B. Because IL-1 is abundant in the KS microenvironment and inhibits KSHV replication, this work may expand our understanding of how KSHV evades host inflammation and immunity for its survival in vivo.