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Journal of Virology, August 2008, p. 7540-7550, Vol. 82, No. 15
0022-538X/08/$08.00+0     doi:10.1128/JVI.00405-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Repeated Passage of Wild-Type Woodchuck Hepatitis Virus in Lymphoid Cells Does Not Generate Cell Type-Specific Variants or Alter Virus Infectivity {triangledown}

Patricia M. Mulrooney-Cousins1 and Tomasz I. Michalak1,2*

Molecular Virology and Hepatology Research Group, Division of BioMedical Science,1 Division of Laboratory Medicine, Faculty of Medicine, Health Sciences Centre, Memorial University, St. John's, Newfoundland, Canada2

Received 25 February 2008/ Accepted 13 May 2008

Woodchuck hepatitis virus (WHV), which is closely related to human hepatitis B virus, infects the liver but also invariably establishes persistent infection in the lymphatic system. Although the dose of invading virus appears to be the main factor in determining whether WHV infection is restricted to the lymphatic system or also engages the liver, the nature of WHV lymphotropism remains unclear and a role for a specific lymphotropic variant was not excluded. The availability of woodchuck lymphocyte and hepatocyte cultures susceptible to WHV infection allows investigation of this issue in vitro. We hypothesized that repeated passage of wild-type WHV in lymphoid cells should lead to enrichment of a lymphotropic virus variant, if in fact such a variant exists. For this purpose, wild-type WHV with a homogeneous sequence was used as the inoculum, while lymphoid cells from a single healthy woodchuck donor and a normal woodchuck WCM-260 hepatocyte line served as infection targets. The serial passage of the wild-type virus repeated up to 13 times for both cell types did not lead to the emergence of cell type-specific WHV variants, as revealed by sequence analysis of the virus envelope and the core and X gene sequences. Moreover, the virus passaged in both cell types remained infectious for naive woodchucks, produced infection profiles that depended upon virus dose but not on virus cellular origin, and retained its initial DNA sequence. These results imply that WHV lymphotropism is a natural propensity of the wild-type virus and is not a consequence of infection with a viral variant.

* Corresponding author. Mailing address: Molecular Virology and Hepatology Research Group, Faculty of Medicine, Health Science Centre, Memorial University, St. John's, Newfoundland, Canada A1B 3V6. Phone: (709) 777-7301. Fax: (709) 777-8279. E-mail: timich{at}mun.ca

{triangledown} Published ahead of print on 21 May 2008.

Journal of Virology, August 2008, p. 7540-7550, Vol. 82, No. 15
0022-538X/08/$08.00+0     doi:10.1128/JVI.00405-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

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  • Gujar, S. A., Michalak, T. I. (2009). Primary Occult Hepadnavirus Infection Induces Virus-Specific T-Cell and Aberrant Cytokine Responses in the Absence of Antiviral Antibody Reactivity in the Woodchuck Model of Hepatitis B Virus Infection. J. Virol. 83: 3861-3876 [Abstract] [Full Text]  


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