Rhesus macaque rhadinovirus encodes a viral interferon regulatory factor to disrupt promyelocytic leukemia nuclear bodies and antagonize type I interferon signaling

Laura K. Springgay, Kristin Fitzpatrick, Byung Park, Ryan Estep, Scott Wong

Research output: Contribution to journalArticle

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. IMPORTANCE KSHV and RRV encode a unique set of homologs of cellular IFN regulatory factors, termed vIRFs, which are hypothesized to help these viruses evade the innate immune response and establish infections in their respective hosts. Our work elucidates the role of one RRV vIRF, R12, and demonstrates that RRV can dampen the type I IFN response downstream of IFN signaling, which would be important for establishing a successful infection in vivo.

Original languageEnglish (US)
Article numbere02147-18
JournalJournal of virology
Volume93
Issue number6
DOIs
StatePublished - Mar 1 2019

Fingerprint

Rhadinovirus
Somatotypes
Interferon Type I
interferons
Macaca mulatta
leukemia
Leukemia
Interferons
Human herpesvirus 8
Human Herpesvirus 8
Interferon Receptors
gene induction
Viruses
viruses
Genes
Infection
Interferon Regulatory Factors
viral interferon regulatory factors
interferon regulatory factors
infection

Keywords

  • Gammaherpesvirus
  • Innate immunity
  • Interferon
  • PML
  • R12
  • Rhadinovirus
  • vIRF

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Rhesus macaque rhadinovirus encodes a viral interferon regulatory factor to disrupt promyelocytic leukemia nuclear bodies and antagonize type I interferon signaling. / Springgay, Laura K.; Fitzpatrick, Kristin; Park, Byung; Estep, Ryan; Wong, Scott.

In: Journal of virology, Vol. 93, No. 6, e02147-18, 01.03.2019.

Research output: Contribution to journalArticle

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