PMID- 30456659
OWN - NLM
STAT- MEDLINE
DCOM- 20190624
LR  - 20200225
IS  - 1995-820X (Electronic)
IS  - 1674-0769 (Print)
IS  - 1995-820X (Linking)
VI  - 34
IP  - 2
DP  - 2019 Apr
TI  - MicroRNA-135a Modulates Hepatitis C Virus Genome Replication through 
      Downregulation of Host Antiviral Factors.
PG  - 197-210
LID - 10.1007/s12250-018-0055-9 [doi]
AB  - Cellular microRNAs (miRNAs) have been shown to modulate HCV infection via 
      directly acting on the viral genome or indirectly through targeting the 
      virus-associated host factors. Recently we generated a comprehensive map of 
      HCV-miRNA interactions through genome-wide miRNA functional screens and 
      transcriptomics analyses. Many previously unappreciated cellular miRNAs were 
      identified to be involved in HCV infection, including miR-135a, a human 
      cancer-related miRNA. In the present study, we investigated the role of miR-135a 
      in regulating HCV life cycle and showed that it preferentially enhances viral 
      genome replication. Bioinformatics-based integrative analyses and subsequent 
      functional assays revealed three antiviral host factors, including receptor 
      interacting serine/threonine kinase 2 (RIPK2), myeloid differentiation primary 
      response 88 (MYD88), and C-X-C motif chemokine ligand 12 (CXCL12), as bona fide 
      targets of miR-135a. These genes have been shown to inhibit HCV infection at the 
      RNA replication stage. Our data demonstrated that repression of key host 
      restriction factors mediated the proviral effect of miR-135a on HCV propagation. 
      In addition, miR-135a hepatic abundance is upregulated by HCV infection in both 
      cultured hepatocytes and human liver, likely mediating a more favorable 
      environment for viral replication and possibly contributing to HCV-induced liver 
      malignancy. These results provide novel insights into HCV-host interactions and 
      unveil molecular pathways linking miRNA biology to HCV pathogenesis.
FAU - Sodroski, Catherine
AU  - Sodroski C
AD  - Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney 
      Diseases, National Institutes of Health, Bethesda, 20892, USA.
FAU - Lowey, Brianna
AU  - Lowey B
AD  - Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney 
      Diseases, National Institutes of Health, Bethesda, 20892, USA.
FAU - Hertz, Laura
AU  - Hertz L
AD  - Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney 
      Diseases, National Institutes of Health, Bethesda, 20892, USA.
FAU - Jake Liang, T
AU  - Jake Liang T
AUID- ORCID: 0000-0003-3828-702X
AD  - Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney 
      Diseases, National Institutes of Health, Bethesda, 20892, USA. 
      jakel@bdg10.niddk.nih.gov.
FAU - Li, Qisheng
AU  - Li Q
AUID- ORCID: 0000-0002-4181-1972
AD  - Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney 
      Diseases, National Institutes of Health, Bethesda, 20892, USA. 
      liqisheng@niddk.nih.gov.
LA  - eng
PT  - Journal Article
DEP - 20181119
PL  - Netherlands
TA  - Virol Sin
JT  - Virologica Sinica
JID - 101514185
RN  - 0 (CXCL12 protein, human)
RN  - 0 (Chemokine CXCL12)
RN  - 0 (MIRN135 microRNA, human)
RN  - 0 (MYD88 protein, human)
RN  - 0 (MicroRNAs)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - EC 2.7.11.1 (RIPK2 protein, human)
RN  - EC 2.7.11.1 (Receptor-Interacting Protein Serine-Threonine Kinase 2)
SB  - IM
MH  - Chemokine CXCL12/genetics
MH  - Down-Regulation
MH  - *Genome, Viral
MH  - Hepacivirus/*pathogenicity/physiology
MH  - Hepatitis C/pathology
MH  - Hepatocytes/virology
MH  - Host-Pathogen Interactions
MH  - Humans
MH  - Liver/virology
MH  - Liver Neoplasms/etiology/virology
MH  - MicroRNAs/*genetics
MH  - Myeloid Differentiation Factor 88/genetics
MH  - Receptor-Interacting Protein Serine-Threonine Kinase 2/genetics
MH  - Transcriptional Activation
MH  - *Virus Replication
PMC - PMC6513812
OTO - NOTNLM
OT  - Antiviral factors
OT  - Genome replication
OT  - Hepatitis C virus (HCV)
OT  - Virus-host interactions
OT  - miR-135a
COIS- CONFLICT OF INTEREST: The authors declare that they have no conflict of interest. 
      ANIMAL AND HUMAN RIGHTS STATEMENT: All patients that provided liver biopsies for 
      this study submitted written informed consent and the protocol was approved by 
      the Institutional Review Board of the National Institute of Diabetes and 
      Digestive and Kidney Diseases (NIDDK) and the National Institute of Arthritis and 
      Musculoskeletal and Skin Diseases (NIAMS). The procedures followed were in 
      accordance with the ethical standards of the institutional committees on human 
      experimentation.
EDAT- 2018/11/21 06:00
MHDA- 2019/06/25 06:00
PMCR- 2018/11/19
CRDT- 2018/11/21 06:00
PHST- 2018/07/24 00:00 [received]
PHST- 2018/09/13 00:00 [accepted]
PHST- 2018/11/21 06:00 [pubmed]
PHST- 2019/06/25 06:00 [medline]
PHST- 2018/11/21 06:00 [entrez]
PHST- 2018/11/19 00:00 [pmc-release]
AID - 10.1007/s12250-018-0055-9 [pii]
AID - 55 [pii]
AID - 10.1007/s12250-018-0055-9 [doi]
PST - ppublish
SO  - Virol Sin. 2019 Apr;34(2):197-210. doi: 10.1007/s12250-018-0055-9. Epub 2018 Nov 
      19.