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Journal of Virology, December 2004, p. 13779-13792, Vol. 78, No. 24
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.24.13779-13792.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Intrahepatic Gene Expression during Chronic Hepatitis C Virus Infection in Chimpanzees{dagger}

Catherine B. Bigger,1,{ddagger} Bernadette Guerra,1 Kathleen M. Brasky,2 Gene Hubbard,2 Michael R. Beard,3,§ Bruce A. Luxon,4 Stanley M. Lemon,3 and Robert E. Lanford1*

Department of Virology and Immunology,1 Department of Comparative Medicine, Southwest National Primate Research Center, Southwest Foundation for Biomedical Research, San Antonio,2 Department of Microbiology and Immunology,3 Bioinformatics Group, University of Texas Medical Branch, Galveston, Texas4

Received 11 May 2004/ Accepted 30 July 2004

Hepatitis C virus (HCV) infections represent a global health problem and are a major contributor to end-stage liver disease including cirrhosis and hepatocellular carcinoma. An improved understanding of the parameters involved in disease progression is needed to develop better therapies and diagnostic markers of disease manifestation. To better understand the dynamics of host gene expression resulting from persistent virus infection, DNA microarray analyses were conducted on livers from 10 chimpanzees persistently infected with HCV. A total of 162 genes were differentially regulated in chronically infected animals compared to uninfected controls. Many genes exhibited a remarkable consistency in changes in expression in the 10 chronically infected animals. A second method of analysis identified 971 genes altered in expression during chronic infection at a 99% confidence level. As with acute-resolving HCV infections, many interferon (IFN)-stimulated genes (ISGs) were transcriptionally elevated, suggesting an ongoing response to IFN and/or double-stranded RNA which is amplified in downstream ISG expression. Thus, persistent infection with HCV results in a complex and partially predictable pattern of gene expression, although the underlying mechanisms regulating the different pathways are not well defined. A single genotype 3-infected animal was available for analysis, and this animal exhibited reduced levels of ISG expression compared to levels of expression with genotype 1 infections and increased expression of a number of genes potentially involved in steatosis. Gene expression data in concert with other observations from HCV infections permit speculation on the regulation of specific aspects of HCV infection.

* Corresponding author. Mailing address: Department of Virology and Immunology, Southwest Foundation for Biomedical Research, 7620 NW Loop 410, San Antonio, TX 78227. Phone: (210) 258-9445. Fax: (210) 670-3329. E-mail: rlanford{at}icarus.sfbr.org.

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

{ddagger} Present address: Children's Research Institute, Columbus, OH 45205.

§ Present address: Department of Molecular Biosciences, The University of Adelaide, North Terrace, Adelaide 5005, South Australia, Australia.

Journal of Virology, December 2004, p. 13779-13792, Vol. 78, No. 24
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.24.13779-13792.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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