PMID- 25520507
OWN - NLM
STAT- MEDLINE
DCOM- 20150420
LR  - 20181113
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 89
IP  - 5
DP  - 2015 Mar
TI  - A human herpesvirus 6A-encoded microRNA: role in viral lytic replication.
PG  - 2615-27
LID - 10.1128/JVI.02007-14 [doi]
AB  - Human herpesvirus 6A (HHV-6A), a member of the betaherpesvirus family, is 
      associated with several human diseases. Like all herpesviruses, HHV-6A 
      establishes a lifelong, latent infection in its host. Reactivation of HHV-6A is 
      frequent within the immunosuppressed and immunocompromised populations and 
      results in lytic viral replication within multiple organs, often leading to 
      severe disease. MicroRNAs (miRNAs) are key regulators of multiple cellular 
      processes that regulate the translation of specific transcripts. miRNAs carried 
      by herpesviruses play important roles in modulating the host cell, thereby 
      facilitating a suitable environment for productive viral infection and/or 
      latency. Currently, there are approximately 150 known human herpesvirus-encoded 
      miRNAs, although an miRNA(s) encoded by HHV-6A has yet to be reported. We 
      hypothesized that HHV-6A, like other members of the human herpesvirus family, 
      encodes miRNAs, which function to promote viral infection. We utilized deep 
      sequencing of small RNA species isolated from cells harboring HHV-6A to identify 
      five novel small noncoding RNA species that originate from the viral genome, one 
      of which has the characteristics of a viral miRNA. These RNAs are expressed 
      during productive infection by either bacterial artificial chromosome 
      (BAC)-derived virus in Jjhan cells or wild-type HHV-6A strain U1102 virus in HSB2 
      cells and are associated with the RNA induced silencing complex (RISC) machinery. 
      Growth analyses of mutant viruses that lack each individual miRNA revealed that a 
      viral miRNA candidate (miR-U86) targets the HHV-6A IE gene U86, thereby 
      regulating lytic replication. The identification and biological characterization 
      of this HHV-6A-specific miRNA is the first step to defining how the virus 
      regulates its life cycle. IMPORTANCE: A majority of the human population is 
      infected with human herpesvirus 6A (HHV-6A), a betaherpesvirus family member. 
      Infections usually occur in young children, and upon resolution, the virus 
      remains in a latent state within the host. Importantly, during times of weakened 
      immune responses, the virus can reactivate and is correlated with significant 
      disease states. Viruses encode many different types of factors that both 
      undermine the host antiviral response and regulate viral replication, including 
      small RNA species called microRNAs (miRNAs). Here we report that HHV-6A encodes 
      at least one miRNA, which we named miR-U86. We have characterized the requirement 
      of this viral miRNA and its impact on the viral life cycle and found that it 
      functions to regulate a viral protein important for efficient viral replication. 
      Our data suggest that viral miRNAs are important for HHV-6A and that they may 
      serve as an important therapeutic target to inhibit the virus.
CI  - Copyright (c) 2015, American Society for Microbiology. All Rights Reserved.
FAU - Nukui, Masatoshi
AU  - Nukui M
AD  - Department of Molecular Genetics, Lerner Research Institute, Cleveland Clinic, 
      Cleveland, Ohio, USA.
FAU - Mori, Yasuko
AU  - Mori Y
AD  - Division of Clinical Virology, Kobe University Graduate School of Medicine, Kobe, 
      Japan.
FAU - Murphy, Eain A
AU  - Murphy EA
AD  - Department of Molecular Genetics, Lerner Research Institute, Cleveland Clinic, 
      Cleveland, Ohio, USA murphye@ccf.org.
LA  - eng
GR  - R01 AI101080/AI/NIAID NIH HHS/United States
GR  - U54 AI057160/AI/NIAID NIH HHS/United States
GR  - RAI101080A/PHS HHS/United States
GR  - U54AI057160/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20141217
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (MicroRNAs)
RN  - 0 (RNA, Viral)
SB  - IM
MH  - Cell Line
MH  - Gene Expression Profiling
MH  - Herpesvirus 6, Human/genetics/*physiology
MH  - High-Throughput Nucleotide Sequencing
MH  - Humans
MH  - MicroRNAs/genetics/*metabolism
MH  - RNA, Viral/genetics/*metabolism
MH  - *Virus Replication
PMC - PMC4325741
EDAT- 2014/12/19 06:00
MHDA- 2015/04/22 06:00
PMCR- 2015/09/01
CRDT- 2014/12/19 06:00
PHST- 2014/12/19 06:00 [entrez]
PHST- 2014/12/19 06:00 [pubmed]
PHST- 2015/04/22 06:00 [medline]
PHST- 2015/09/01 00:00 [pmc-release]
AID - JVI.02007-14 [pii]
AID - 02007-14 [pii]
AID - 10.1128/JVI.02007-14 [doi]
PST - ppublish
SO  - J Virol. 2015 Mar;89(5):2615-27. doi: 10.1128/JVI.02007-14. Epub 2014 Dec 17.