PMID- 27512057
OWN - NLM
STAT- MEDLINE
DCOM- 20170509
LR  - 20181113
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 90
IP  - 20
DP  - 2016 Oct 15
TI  - Japanese Macaque Rhadinovirus Encodes a Viral MicroRNA Mimic of the miR-17 
      Family.
PG  - 9350-63
LID - 10.1128/JVI.01123-16 [doi]
AB  - 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-kappaB) signaling in the presence of two 
      proinflammatory cytokines, tumor necrosis factor alpha (TNF-alpha) and interleukin-1beta 
      (IL-1beta). Multiple JMRV miRNAs suppressed cytokine-induced NF-kappaB 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. IMPORTANCE: 
      Gammaherpesviruses are associated with multiple diseases linked to 
      immunosuppression and inflammation, including AIDS-related cancers and autoimmune 
      diseases. JMRV is a recently identified herpesvirus that has been linked to JME, 
      an inflammatory demyelinating disease in Japanese macaques that mimics multiple 
      sclerosis. There are few large-animal models for gammaherpesvirus-associated 
      pathogenesis. Here, we provide the first experimental evidence of JMRV miRNAs in 
      vitro and demonstrate that one of these viral miRNAs can mimic the activity of 
      the cellular miR-17/20/106 family. Our work provides unique insight into the 
      roles of viral miRNAs during rhadinovirus infection and provides an important 
      step toward understanding viral miRNA function in a nonhuman primate model 
      system.
CI  - Copyright (c) 2016, American Society for Microbiology. All Rights Reserved.
FAU - Skalsky, Rebecca L
AU  - Skalsky RL
AD  - Vaccine and Gene Therapy Institute, Oregon Health & Science University, 
      Beaverton, Oregon, USA skalsky@ohsu.edu.
FAU - Barr, Sarah A
AU  - Barr SA
AD  - Vaccine and Gene Therapy Institute, Oregon Health & Science University, 
      Beaverton, Oregon, USA.
FAU - Jeffery, Andrew J
AU  - Jeffery AJ
AD  - Vaccine and Gene Therapy Institute, Oregon Health & Science University, 
      Beaverton, Oregon, USA.
FAU - Blair, Tiffany
AU  - Blair T
AD  - Vaccine and Gene Therapy Institute, Oregon Health & Science University, 
      Beaverton, Oregon, USA.
FAU - Estep, Ryan
AU  - Estep R
AD  - Vaccine and Gene Therapy Institute, Oregon Health & Science University, 
      Beaverton, Oregon, USA.
FAU - Wong, Scott W
AU  - Wong SW
AD  - Vaccine and Gene Therapy Institute, Oregon Health & Science University, 
      Beaverton, Oregon, USA.
LA  - eng
GR  - P51 OD011092/OD/NIH HHS/United States
GR  - R01 CA075922/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20160929
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (3' Untranslated Regions)
RN  - 0 (Interleukin-1beta)
RN  - 0 (MicroRNAs)
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Viral)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - 3' Untranslated Regions/genetics
MH  - Animals
MH  - Base Sequence
MH  - Cell Line
MH  - Demyelinating Diseases/genetics/virology
MH  - Encephalomyelitis/genetics/virology
MH  - Gene Expression Profiling/methods
MH  - HEK293 Cells
MH  - Herpesviridae Infections/genetics/virology
MH  - Herpesvirus 8, Human/genetics
MH  - High-Throughput Nucleotide Sequencing
MH  - Humans
MH  - Interleukin-1beta/genetics
MH  - Japan
MH  - Macaca/*virology
MH  - MicroRNAs/*genetics
MH  - NF-kappa B/genetics
MH  - RNA, Viral/*genetics
MH  - Rhadinovirus/*genetics
MH  - Sequence Homology
MH  - Tumor Necrosis Factor-alpha/genetics
PMC - PMC5044857
EDAT- 2016/08/12 06:00
MHDA- 2017/05/10 06:00
PMCR- 2017/03/29
CRDT- 2016/08/12 06:00
PHST- 2016/06/09 00:00 [received]
PHST- 2016/08/01 00:00 [accepted]
PHST- 2016/08/12 06:00 [entrez]
PHST- 2016/08/12 06:00 [pubmed]
PHST- 2017/05/10 06:00 [medline]
PHST- 2017/03/29 00:00 [pmc-release]
AID - JVI.01123-16 [pii]
AID - 01123-16 [pii]
AID - 10.1128/JVI.01123-16 [doi]
PST - epublish
SO  - J Virol. 2016 Sep 29;90(20):9350-63. doi: 10.1128/JVI.01123-16. Print 2016 Oct 
      15.