Japanese macaque rhadinovirus encodes a viral microRNA mimic of the miR-17 family

Rebecca Skalsky, Sarah A. Barr, Andrew J. Jeffery, Tiffany Blair, Ryan Estep, Scott Wong

Research output: Contribution to journalArticle

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Abstract

Japanese macaque (JM) rhadinovirus (JMRV) is a novel, gamma-2 herpesvirus that was recently isolated from JM with inflammatory demyelinating encephalomyelitis (JME). JME is a spontaneous and chronic disease with clinical characteristics and immunohistopathology comparable to those of multiple sclerosis in humans. Little is known about the molecular biology of JMRV. Here, we sought to identify and characterize the small RNAs expressed during lytic JMRV infection using deep sequencing. Fifteen novel viral microRNAs (miRNAs) were identified in JMRV-infected fibroblasts, all of which were readily detectable by 24 h postinfection and accumulated to high levels by 72 h. Sequence comparisons to human Kaposi's sarcoma-associated herpesvirus (KSHV) miRNAs revealed several viral miRNA homologs. To functionally characterize JMRV miRNAs, we screened for their effects on nuclear factor kappa B (NF-κB) signaling in the presence of two proinflammatory cytokines, tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β). Multiple JMRV miRNAs suppressed cytokine-induced NF-κB activation. One of these miRNAs, miR-J8, has seed sequence homology to members of the cellular miR-17/20/106 and miR-373 families, which are key players in cell cycle regulation as well as inflammation. Using reporters, we show that miR-J8 can target 3' untranslated regions (UTRs) with miR-17-5p or miR-20a cognate sites. Our studies implicate JMRV miRNAs in the suppression of innate antiviral immune responses, which is an emerging feature of many viral miRNAs.

Original languageEnglish (US)
Pages (from-to)9350-9363
Number of pages14
JournalJournal of Virology
Volume90
Issue number20
DOIs
StatePublished - 2016

Fingerprint

Rhadinovirus
Macaca fuscata
Macaca
MicroRNAs
microRNA
NF-kappa B
cytokines
Human herpesvirus 8
Cytokines
Encephalomyelitis
High-Throughput Nucleotide Sequencing
Human Herpesvirus 8
Herpesviridae
interleukin-1
sclerosis
3' Untranslated Regions
3' untranslated regions
encephalitis
Sequence Homology
sequence homology

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Japanese macaque rhadinovirus encodes a viral microRNA mimic of the miR-17 family. / Skalsky, Rebecca; Barr, Sarah A.; Jeffery, Andrew J.; Blair, Tiffany; Estep, Ryan; Wong, Scott.

In: Journal of Virology, Vol. 90, No. 20, 2016, p. 9350-9363.

Research output: Contribution to journalArticle

Skalsky, Rebecca ; Barr, Sarah A. ; Jeffery, Andrew J. ; Blair, Tiffany ; Estep, Ryan ; Wong, Scott. / Japanese macaque rhadinovirus encodes a viral microRNA mimic of the miR-17 family. In: Journal of Virology. 2016 ; Vol. 90, No. 20. pp. 9350-9363.
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