Viral interferon regulatory factors are critical for delay of the host immune response against rhesus macaque rhadinovirus infection

Bridget A. Robinson, Megan A. O'connor, He Li, Flora Engelmann, Britt Poland, Richard Grant, Victor Defilippis, Ryan D. Estep, Michael K. Axthelm, Ilhem Messaoudi, Scott W. Wong

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Kaposi's sarcoma-associated herpesvirus (KSHV) and the closely related gamma-2 herpesvirus rhesus macaque (RM) rhadinovirus (RRV) are the only known viruses to encode viral homologues of the cellular interferon (IFN) regulatory factors (IRFs). Recent characterization of a viral IRF (vIRF) deletion clone of RRV (vIRF-knockout RRV [vIRF-ko RRV]) demonstrated that vIRFs inhibit induction of type I and type II IFNs during RRV infection of peripheral blood mononuclear cells. Because the IFN response is a key component to a host's antiviral defenses, this study has investigated the role of vIRFs in viral replication and the development of the immune response during in vivo infection in RMs, the natural host of RRV. Experimental infection of RMs with vIRF-ko RRV resulted in decreased viral loads and diminished B cell hyperplasia, a characteristic pathology during acute RRV infection that often develops into more severe lymphoproliferative disorders in immune-compromised animals, similar to pathologies in KSHV-infected individuals. Moreover, in vivo infection with vIRF-ko RRV resulted in earlier and sustained production of proinflammatory cytokines and earlier induction of an anti-RRV T cell response compared to wild-type RRV infection. These findings reveal the broad impact that vIRFs have on pathogenesis and the immune response in vivo and are the first to validate the importance of vIRFs during de novo infection in the host.

Original languageEnglish (US)
Pages (from-to)2769-2779
Number of pages11
JournalJournal of virology
Volume86
Issue number5
DOIs
StatePublished - Mar 1 2012

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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    Robinson, B. A., O'connor, M. A., Li, H., Engelmann, F., Poland, B., Grant, R., Defilippis, V., Estep, R. D., Axthelm, M. K., Messaoudi, I., & Wong, S. W. (2012). Viral interferon regulatory factors are critical for delay of the host immune response against rhesus macaque rhadinovirus infection. Journal of virology, 86(5), 2769-2779. https://doi.org/10.1128/JVI.05657-11