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Hepatitis C virus NS4A and NS4B proteins suppress translation in vivo
Author(s) -
Kato Jun,
Kato Naoya,
Yoshida Hideo,
OnoNita Suzane Kioko,
Shiratori Yasushi,
Omata Masao
Publication year - 2002
Publication title -
journal of medical virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.782
H-Index - 121
eISSN - 1096-9071
pISSN - 0146-6615
DOI - 10.1002/jmv.2129
Subject(s) - internal ribosome entry site , ns5a , ns5b , protein biosynthesis , ns2 3 protease , ns3 , virology , biology , hepatitis c virus , translation (biology) , microbiology and biotechnology , virus , messenger rna , hepacivirus , gene , biochemistry
Many viruses can inhibit protein synthesis in their host cells by targeting translation (“translational shutoff”). There are few reports on the effects of hepatitis C virus (HCV) infection on protein synthesis, because of the lack of a reproducible tissue culture system for HCV. In this study, the influence of seven HCV proteins (core, NS2, NS3, NS4A, NS4B, NS5A, NS5B) on protein synthesis was examined using a reporter assay. In addition, it was determined whether the HCV proteins inhibit protein synthesis via transcription or translation using an RNase protection assay and the effect of HCV proteins on translation from the HCV internal ribosome entry site (IRES) was also examined using a bicistronic reporter. Of the seven HCV proteins, NS4A and NS4B proteins inhibited cellular protein synthesis by targeting the process of translation. They also inhibited translation from the HCV IRES. Moreover, NS4A protein, induced under the control of doxycycline, inhibited the proliferation of HeLa cells. In conclusion, HCV NS4A and NS4B proteins have an effect of translational inhibition. This novel function may be involved in HCV infection and help its survival in host cells. J. Med. Virol. 66:187–199, 2002. © 2002 Wiley‐Liss, Inc.