Rhesus Macaque Rhadinovirus Encodes a Viral Interferon Regulatory Factor To Disrupt Promyelocytic Leukemia Nuclear Bodies and Antagonize Type I Interferon Signaling

Authors

Laura K. Springgay, Oregon Health & Science University
Kristin Fitzpatrick, Vaccine & Gene Therapy Institute
Byung Park, OHSU-PSU School of Public HealthFollow
Ryan D. Estep, Vaccine & Gene Therapy Institute
Scott W. Wong, Oregon Health & Science UniversityFollow

Sponsor

Public Health Service (PHS) grant P51-OD011092 supports the ONPRC Flow Cytometry, Bioinformatics & Biostatistics, and Imaging and Morphology Support Cores. This study was supported by PHS grants P51-OD011092 (S.W.W.), CA075922 (S.W.W.), and CA206404 (S.W.W.). L.K.S. was supported by the ARCS Foundation Portland Chapter and by training grants T32 AI074494 and T32 AI007472.

Published In

Journal of Virology

Document Type

Citation

Publication Date

1-1-2019

Abstract

Interferon (IFN) production and the subsequent induction of IFN-stimulated genes (ISGs) are highly effective innate strategies utilized by cells to protect against invading pathogens, including viruses. Critical components involved in this innate process are promyelocytic leukemia nuclear bodies (PML-NBs), which are subnuclear structures required for the development of a robust IFN response. As such, PML-NBs serve as an important hurdle for viruses to overcome to successfully establish an infection. Both Kaposi's sarcoma-associated herpesvirus (KSHV) and the closely related rhesus macaque rhadinovirus (RRV) are unique for encoding viral homologs of IFN regulatory factors (termed vIRFs) that can manipulate the host immune response by multiple mechanisms. All four KSHV vIRFs inhibit the induction of IFN, while vIRF1 and vIRF2 can inhibit ISG induction downstream of the IFN receptor. Less is known about the RRV vIRFs. RRV vIRF R6 can inhibit the induction of IFN by IRF3; however, it is not known whether any RRV vIRFs inhibit ISG induction following IFN receptor signaling. In our present study, we demonstrate that the RRV vIRF R12 aids viral replication in the presence of the type I IFN response. This is achieved in part through the disruption of PML-NBs and the inhibition of robust ISG transcription.

Description

Copyright © 2019 American Society for Microbiology

Locate the Document

http://doi.org/10.1128/JVI.02147-18

DOI

10.1128/JVI.02147-18

Persistent Identifier

https://archives.pdx.edu/ds/psu/28030

Citation Details

Laura K. Springgay, Kristin Fitzpatrick, Byung Park, Ryan D. Estep, Scott W. Wong. (2019). Rhesus Macaque Rhadinovirus Encodes a Viral Interferon Regulatory Factor To Disrupt Promyelocytic Leukemia Nuclear Bodies and Antagonize Type I Interferon Signaling Journal of Virology, 93 (6) e02147-18.