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Journal of Virology, March 2008, p. 2241-2249, Vol. 82, No. 5
0022-538X/08/$08.00+0     doi:10.1128/JVI.02093-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Hepatitis C Virus Genotype 1a Growth and Induction of Autophagy{triangledown}

Malika Ait-Goughoulte,1 Tatsuo Kanda,1 Keith Meyer,1 Jan S. Ryerse,2 Ratna B. Ray,2 and Ranjit Ray1,3*

Departments of Internal Medicine,1 Pathology,2 Molecular Microbiology and Immunology, Saint Louis University, St. Louis, Missouri3

Received 20 September 2007/ Accepted 2 December 2007

We have previously reported that immortalized human hepatocytes (IHH) support the generation of infectious hepatitis C virus (HCV) genotype 1a (clone H77). In the present study, we have investigated the growth of HCV genotype 1a (clone H77) through serial passages and accompanying changes in IHH in response to infection. Eleven serial passages of HCV genotype 1a (clone H77) in IHH were completed. Virus replication was ascertained from the presence of HCV-specific sequences, the detection of core antigen, the virus genome copy number, and the virus titer in IHH culture fluid. Electron microscopy suggested that HCV infection induces autophagic vacuole formation in IHH. Fluorescence microscopy displayed localization of autophagic markers, microtubule-associated protein-1 light chain-3 and Apg5, on the vacuoles of HCV-infected hepatocytes. Taken together, our results suggested that HCV genotype 1a (clone H77) can be serially passaged in IHH and that HCV infection induces an autophagic response in hepatocytes.

* Corresponding author. Mailing address: Division of Infectious Diseases and Immunology, Center for Vaccine Development, Edward A. Doisy Research Center, 1100 S. Grand Blvd., 8th Floor, St. Louis, MO 63104. Phone: (314) 977-9034. Fax: (314) 771-3816. E-mail: rayr{at}slu.edu

{triangledown} Published ahead of print on 12 December 2007.

Journal of Virology, March 2008, p. 2241-2249, Vol. 82, No. 5
0022-538X/08/$08.00+0     doi:10.1128/JVI.02093-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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