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Journal of Virology, November 2001, p. 11017-11024, Vol. 75, No. 22
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.22.11017-11024.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Identification of a Hepatic Factor Capable of Supporting Hepatitis C Virus Replication in a Nonpermissive Cell Line

Chau-Ting Yeh,1,* Hsin-Yu Lai,1 Tse-Ching Chen,2 Chia-Ming Chu,1 and Yun-Fan Liaw1

Liver Research Unit1 and Department of Pathology,2 Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taipei, Taiwan

Received 11 June 2001/Accepted 16 August 2001

Although hepatitis C virus E2 protein can bind to human cells by interacting with a putative viral receptor, CD81, the interaction alone is not sufficient to establish permissiveness for hepatitis C virus infection. Using an Epstein-Barr virus-based extrachromosomal replication system, we have screened through a human liver cDNA library and successfully identified a cDNA capable of supporting hepatitis C virus replication in an otherwise nonpermissive cell line. This cDNA encodes a protein exhibiting homology to a group of proteins derived from various evolutionarily distant species, including Oryza sativa submergence-induced protein 2A. The mRNAs encoding this factor are heterogeneous at the 5' ends and are ubiquitously expressed in multiple tissues, albeit in a very small amount. The longest mRNA contains an in-frame and upstream initiation codon and codes for a larger protein. This 5'-extended form of mRNA was detected in hepatocellular carcinoma, but not in normal liver tissue. Immunofluorescence analysis demonstrated that the hepatic factor was distributed evenly in cells, but occasionally formed aggregations in the peri- or intranuclear areas. In summary, we have identified a hepatic factor capable of supporting hepatitis C virus replication in an otherwise nonpermissive cell line. This factor belongs to a previously uncharacterized protein family. The physiological function of this protein awaits further study.

* Corresponding author. Mailing address: Liver Research Unit, Chang Gung Memorial Hospital, 199 Tung Hwa North Rd., Taipei 105, Taiwan. Phone: 886-3-3281200, ext. 8120. Fax: 886-3-3282824. E-mail: catyeh{at}ms14.hinet.net.

Journal of Virology, November 2001, p. 11017-11024, Vol. 75, No. 22
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.22.11017-11024.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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