Gene expression profiling indicates the roles of host oxidative stress, apoptosis, lipid metabolism, and intracellular transport genes in the replication of hepatitis C virus.
Hepatitis C virus (HCV) is a leading cause of chronic liver disease. The identification and characterization of key host cellular factors that play a role in the HCV replication cycle are important for the understanding of disease pathogenesis and the identification of novel antiviral therapeutic targets. Gene expression profiling of JFH-1-infected Huh7 cells by microarray analysis was performed to identify host cellular genes that are transcriptionally regulated by infection. The expression of host genes involved in cellular defense mechanisms (apoptosis, proliferation, and antioxidant responses), cellular metabolism (lipid and protein metabolism), and intracellular transport (vesicle trafficking and cytoskeleton regulation) was significantly altered by HCV infection. The gene expression patterns identified provide insight into the potential mechanisms that contribute to HCV-associated pathogenesis. These include an increase in proinflammatory and proapoptotic signaling and a decrease in the antioxidant response pathways of the infected cell. To investigate whether any of the host genes regulated by infection were required by HCV during replication, small interfering RNA (siRNA) silencing of host gene expression in HCV-infected cells was performed. Decreasing the expression of host genes involved in lipid metabolism (TXNIP and CYP1A1 genes) and intracellular transport (RAB33b and ABLIM3 genes) reduced the replication and secretion of HCV, indicating that they may be important factors for the virus replication cycle. These results show that major changes in the expression of many different genes in target cells may be crucial in determining the outcome of HCV infection.
Blackham
Samantha
S
Department of Hepatology, Faculty of Medicine, Imperial College London, St. Mary's Campus, Norfolk Place, London W2 1PG, United Kingdom.
Baillie
Andrew
A
Al-Hababi
Fadel
F
Remlinger
Katja
K
You
Shihyun
S
Hamatake
Robert
R
McGarvey
Michael J
MJ
D017209:Apoptosis; D002460:Cell Line; D020869:Gene Expression Profiling; D016174:Hepacivirus / Q000472:pathogenicity* / Q000502:physiology*; D022781:Hepatocytes / Q000821:virology*; D054884:Host-Pathogen Interactions; D006801:Humans; D050356:Lipid Metabolism; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress; D021381:Protein Transport; D014779:Virus Replication