Identification of a specific gene expression pattern associated with HCV-induced pathogenesis in HCV- and HCV/HIV-infected individuals.
Gene expression profiling was performed on liver biopsies from 28 patients (12 HCV and 16 HCV/HIV infected) in an attempt to understand the mechanisms of HCV liver disease in the presence and absence of HIV coinfection. The data were compared with clinical observations and a gene expression database obtained for transplant HCV-infected samples. This is the first report of functional genomics being used to compare intrahepatic gene expression profiles of HCV- and HCV/HIV-infected individuals. Significantly, the intrahepatic global gene expression profiles do not differ between HCV- and HCV/HIV-infected individuals. However, a subset of patients was identified who share a specific pattern of gene expression, termed the enhanced gene expression (EGE) pattern. Specifically, the EGE (+) patients show a dramatic decreased expression of multiple genes associated with the FAS-apoptosis pathway and increased expression of lymphocyte adhesion molecules and lymphocyte-specific genes. The EGE (+) patients also have partially impaired Type I and II IFN-mediated antiviral responses, including a lack of induction of the anti-fibrogenic cytokine IFN-gamma. Importantly, the pattern of gene expression observed in EGE (+) patients has similarities to patients who developed fibrosis within 1 year of receiving a liver transplant.
Department of Microbiology, School of Medicine, University of Washington, Box 358070, Seattle, WA 98195-8070, USA. kathiw@u.washington.edu
Kathie-Anne
KA
Walters
Maria W
MW
Smith
Sampa
S
Pal
Jill C
JC
Thompson
Matthew J
MJ
Thomas
Matthew M
MM
Yeh
David L
DL
Thomas
Matthew
M
Fitzgibbon
Sean
S
Proll
Nelson
N
Fausto
David R
DR
Gretch
Robert L
RL
Carithers
Margaret C
MC
Shuhart
Michael G
MG
Katze
D005260:Female; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D006678:HIV / Q000235:genetics / Q000472:pathogenicity; D015658:HIV Infections / Q000150:complications*; D016174:Hepacivirus / Q000235:genetics* / Q000472:pathogenicity*; D006526:Hepatitis C / Q000150:complications*; D006801:Humans; D017403:In Situ Hybridization; D007372:Interferons / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000235:genetics / Q000302:isolation & purification
D012367:RNA, Viral; D007372:Interferons