This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental material
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Google Scholar
Right arrow Articles by Machida, K.
Right arrow Articles by Lai, M. M. C.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Machida, K.
Right arrow Articles by Lai, M. M. C.

 Previous Article  |  Next Article 

Journal of Virology, December 2009, p. 12590-12600, Vol. 83, No. 23
0022-538X/09/$08.00+0     doi:10.1128/JVI.02643-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Hepatitis C Virus Causes Uncoupling of Mitotic Checkpoint and Chromosomal Polyploidy through the Rb Pathway {triangledown} ,{dagger}

Keigo Machida,1 Jian-Chang Liu,1 George McNamara,2 Alexandra Levine,3 Lewei Duan,1 and Michael M. C. Lai1,4*

Department of Molecular Microbiology and Immunology, University of Southern California, Keck School of Medicine, Los Angeles, California 90033,1 Saban Research Institute, Los Angeles Children's Hospital, Los Angeles, California,2 City of Hope, Duarte, California,3 Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan4

Received 23 December 2008/ Accepted 8 September 2009

Hepatitis C virus (HCV) infection is associated with the development of hepatocellular carcinoma and probably also non-Hodgkin's B-cell lymphoma. The molecular mechanisms of HCV-associated carcinogenesis are unknown. Here we demonstrated that peripheral blood mononuclear cells obtained from hepatitis C patients and hepatocytes infected with HCV in vitro showed frequent chromosomal polyploidy. HCV infection or the expression of viral core protein alone in hepatocyte culture or transgenic mice inhibited mitotic spindle checkpoint function because of reduced Rb transcription and enhanced E2F-1 and Mad2 expression. The silencing of E2F-1 by RNA interference technology restored the function of mitotic checkpoint in core-expressing cells. Taken together, these data suggest that HCV infection may inhibit the mitotic checkpoint to induce polyploidy, which likely contributes to neoplastic transformation.

* Corresponding author. Mailing address: Department of Molecular Microbiology and Immunology, University of Southern California, Keck School of Medicine, Los Angeles, CA 90033. Phone: (323) 442-1748. Fax: (323) 442-1721. E-mail: michlai{at}usc.edu

{triangledown} Published ahead of print on 30 September 2009.

{dagger} Supplemental material for this article may be found at http://jvi.asm.org/.

Journal of Virology, December 2009, p. 12590-12600, Vol. 83, No. 23
0022-538X/09/$08.00+0     doi:10.1128/JVI.02643-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»