PMID- 24205826
OWN - NLM
STAT- MEDLINE
DCOM- 20151012
LR  - 20211021
IS  - 1365-2893 (Electronic)
IS  - 1352-0504 (Print)
IS  - 1352-0504 (Linking)
VI  - 21
IP  - 10
DP  - 2014 Oct
TI  - Identification of novel human kinases that suppress hepatitis C virus infection.
PG  - 716-26
LID - 10.1111/jvh.12203 [doi]
AB  - The human kinome includes between 500 and 600 known kinases and open reading 
      frames (ORFs) that play key roles in regulating many cellular processes. Past 
      studies adopting loss-of-function approaches have identified some kinases whose 
      activities are required for hepatitis C virus (HCV) life cycle. Here, by 
      screening a retroviral cDNA library of 192 active human kinases, we found that 
      three of them, namely cyclin-dependent kinases regulatory subunit 1 (CKS1B), 
      mitogen-activated protein kinase kinase 5 (MAP2K5) and protein kinase C and 
      casein kinase substrate in neurons 1 (PACSIN1), potently suppressed HCV 
      infection. The expression of these kinases did not induce the production of type 
      I interferon (IFN) and interferon-stimulated genes (ISGs); instead, they 
      inhibited HCV at postentry stages. Specifically, CKS1B and MAP2K5 significantly 
      inhibited viral RNA replication. PACSIN1, by contrast, inhibited HCV infection by 
      decreasing the level of HCV p7. Altogether, the identification of human protein 
      kinases that exert an anti-HCV activity highlighted the potential of combating 
      HCV infection by activating specific kinase-mediated pathways, offering an 
      alternative strategy of treatment.
CI  - (c) 2013 John Wiley & Sons Ltd.
FAU - Lee, A
AU  - Lee A
AD  - Departments of Infectious Diseases and Microbiology, University of Pittsburgh, 
      Pittsburgh, PA, USA.
FAU - Liu, S
AU  - Liu S
FAU - Wang, T
AU  - Wang T
LA  - eng
GR  - R01 DK088787/DK/NIDDK NIH HHS/United States
GR  - R01DK088787/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20131110
PL  - England
TA  - J Viral Hepat
JT  - Journal of viral hepatitis
JID - 9435672
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (CKS1B protein, human)
RN  - 0 (Interferon Type I)
RN  - 0 (PACSIN1 protein, human)
RN  - EC 2.7.11.22 (CDC2-CDC28 Kinases)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 5)
RN  - EC 2.7.12.2 (MAP2K5 protein, human)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing/*metabolism
MH  - CDC2-CDC28 Kinases/*metabolism
MH  - Hepacivirus/immunology/*physiology
MH  - Hepatitis C/*immunology
MH  - *Host-Pathogen Interactions
MH  - Humans
MH  - Interferon Type I/metabolism
MH  - MAP Kinase Kinase 5/*metabolism
MH  - *Virus Replication
PMC - PMC4130908
MID - NIHMS533073
OTO - NOTNLM
OT  - hepatitis C virus
OT  - human kinase
OT  - viral hepatitis
COIS- CONFLICT OF INTEREST The authors have no competing interest.
EDAT- 2013/11/12 06:00
MHDA- 2015/10/13 06:00
PMCR- 2014/10/01
CRDT- 2013/11/12 06:00
PHST- 2013/03/20 00:00 [received]
PHST- 2013/09/17 00:00 [accepted]
PHST- 2013/11/12 06:00 [entrez]
PHST- 2013/11/12 06:00 [pubmed]
PHST- 2015/10/13 06:00 [medline]
PHST- 2014/10/01 00:00 [pmc-release]
AID - 10.1111/jvh.12203 [doi]
PST - ppublish
SO  - J Viral Hepat. 2014 Oct;21(10):716-26. doi: 10.1111/jvh.12203. Epub 2013 Nov 10.