Research Project
Grant-in-Aid for Scientific Research (C)
Development of HCV replicon cells and HCV production system using HCV JFH1 strain enabled us to investigate the whole life cycle of HCV and the host factors essential for HCV production. In this study, we aimed to clarify molecular mechanism of HCV production by investigating binding partners for HCV proteins. We analyzed HCV core-binding proteins, hnRNPH1/H2/F. Addition of HCV RNA inhibited the binding between the core protein and hnRNPs. RNase recovered this inhibition. Theseresults suggest that RNA is required for the interaction between the core protein and hnRNPs. Our results suggest that these hnRNPH and hnRNPF cooperatively regulate HCV replication. We then identified HCV NS5A-binding proteins, ubiquitin ligase p138, transcription factor HNF-1a, and histone methyltransferase SMYD3. The p138 protein bound NS5A protein, but not other HCV proteins. Our data suggest that p138 protein promotes ubiquitylation of NS5A protein and enhances its proteasomal degradation, suggesting that p138 regulates HCV replication. We analyzed the p138-binding domain on the NS5A protein using a series of deletion mutants. Then weanalyzed the ubiquitylation site on the NS5A protein using 13 point-mutants. These studies would contribute to the better understanding of HCV life cycles as well as the viral pathogenesis.
All 2012 2011 2010 Other
All Journal Article (28 results) (of which Peer Reviewed: 28 results) Presentation (36 results) (of which Invited: 1 results) Book (6 results) Remarks (2 results)
World Journal of Virology
Volume: 1 Pages: 44-50
Journal of Virology
Volume: 86(23) Pages: 12903-11
PLoS One
Volume: 7(10)
Frontiers in Microbiology
Volume: 2 Pages: 1-5
Microbes and Infection
Volume: 14 Pages: 69-78
Journal of Medical Virology
Volume: 84 Pages: 229-34
Intervirology
Volume: 55 Pages: 1-11
Volume: 7 Pages: 1-10
World J. Virol.
Volume: 2 Issue: 2 Pages: 44-50
10.5501/wjv.v1.i2.44
J Virol.
Volume: 86 Issue: 23 Pages: 12903-12911
10.1128/jvi.01418-12
Volume: 7(10) Issue: 10 Pages: e46634-e46634
10.1371/journal.pone.0046634
Volume: 84 Issue: 2 Pages: 229-234
10.1002/jmv.22257
Inervirology
Volume: 55 Issue: 1 Pages: 1-11
10.1159/000322219
Volume: 55 Issue: 2 Pages: 1-10
10.1371/journal.pone.0030513
Microbiology and Immunology
Volume: 55 Pages: 418-26
10031121486
Volume: 85 Pages: 8556-68
Virology
Volume: 410 Pages: 38-47
Stem Cells Dev
Volume: 20 Issue: 6 Pages: 1503-1510
10.1111/j.1348-0421.2011.00331.x
J.Virol.
Volume: 85 Issue: 17 Pages: 8556-8568
10.1128/jvi.00146-11
Volume: 54 Pages: 684-90
Journal of Cellular Biochemistry
Volume: 111 Pages: 676-85
Hepatology
Volume: 52 Pages: 411-420
Volume: 82 Pages: 1364-70
Volume: 54 Pages: 684-690
10029546273
Volume: 111 Pages: 676-685
Volume: 82 Pages: 1364-1370
http://www.med.kobe-u.ac.jp/micro/1.htm