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Identification of novel human kinases that suppress hepatitis C virus infection
Author(s) -
Lee A.,
Liu S.,
Wang T.
Publication year - 2014
Publication title -
journal of viral hepatitis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 100
eISSN - 1365-2893
pISSN - 1352-0504
DOI - 10.1111/jvh.12203
Subject(s) - kinome , kinase , casein kinase 1 , biology , interferon , casein kinase 2 , hepatitis c virus , protein kinase r , virology , cyclin dependent kinase 2 , microbiology and biotechnology , protein kinase a , virus
Summary The human kinome includes between 500 and 600 known kinases and open reading frames ( ORF s) 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 c DNA library of 192 active human kinases, we found that three of them, namely cyclin‐dependent kinases regulatory subunit 1 ( CKS 1 B ), mitogen‐activated protein kinase kinase 5 ( MAP 2 K 5) and protein kinase C and casein kinase substrate in neurons 1 ( PACSIN 1), potently suppressed HCV infection. The expression of these kinases did not induce the production of type I interferon ( IFN ) and interferon‐stimulated genes ( ISG s); instead, they inhibited HCV at postentry stages. Specifically, CKS 1 B and MAP 2 K 5 significantly inhibited viral RNA replication. PACSIN 1, 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.