Progress Reported Against Gene Involved in Hepatitis C

WEDNESDAY March 18, 2009 -- Nearly 100 genes that support replication of the hepatitis C virus (HCV) in the human body have been identified by Massachusetts General Hospital researchers.

They also found that blocking several of the genes suppressed replication of the virus.

"We may be a few years away from developing therapies based on these findings, but this study is a proof of principle that targeting host factors is a viable therapeutic strategy," Dr. Andrew Tai, of the hospital's gastrointestinal unit and lead researcher on the study, said in a hospital news release.

Long-term HCV infection can lead to liver failure or liver cancer. Currently, a six- to 11-month regimen of peginterferon and the antiviral drug ribavirin is used to treat HCV, but the therapy can cause serious side effects and is ineffective in many people.

Tai and his colleagues examined whether using small interfering RNAs (siRNAs) to block each of the approximately 21,000 predicted messenger RNA transcripts in the human genome had any effect on HCV replication. The siRNA scan identified 96 genes that appear to play a role in HCV replication, and the researchers took a closer look at several of those genes.

One of the genes encodes for an enzyme called PI4KA, believed to play a role in the formation of membrane structures within the cell that may be the site of HCV replication. Another group of genes contributes to formation of the COPI coat that covers several types of cellular vesicles and plays a role in the replication of poliovirus, the researchers said.

They also zeroed in on the gene for a liver protein (hepcidin) that regulates iron absorption. People with chronic HCV infection experience elevated iron levels in the liver and blood.

Blocking each of these genes prevented HCV replication, as did drugs that inhibit PI4KA and COPI.

Further research is needed to identify the molecular mechanisms in these genes that support HCV replication. That could lead to new treatments for HCV infection, the researchers said.

The study is in the March 19 issue of Cell Host & Microbe.

More information

The American Academy of Family Physicians has more about hepatitis C.

Posted: March 2009


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