Newly discovered gene predicts HCV interferon response

Researchers have discovered a gene which interferes with the clearance of hepatitis C virus (HCV) infection.

The finding helps to explain why African Americans are less likely to respond to interferon treatment than European or Asian patients, and could lead to new treatments.

"We've identified a new gene that may help us better understand response to viral infection and the new genetic marker may transition to clinical practice because it predicts treatment outcome for African-American patients better than the current genetic test," said Thomas O'Brien (National Cancer Institute, Bethesda, Maryland, USA) in a press statement.

The researchers treated human liver cells with a synthetic mimic of HCV RNA to imitate HCV infection and carried out RNA sequencing.

The novel gene was discovered in a region of the genome already known to contain the genes for several types of interferons which suppress HCV replication. Variation in this region has already been strongly associated with HCV clearance.

The newly named IFNL4 is created by a single base deletion in the DNA, resulting in expression of a protein not found in the cells of those without the deletion.

Using data from previous studies of HCV-infected patients, the authors show that the expression of the INFL4 protein is associated with poorer clearance of the virus and poorer response to pegylated interferon and ribavirin treatment than those without the allele.

An alternative allele, that includes an additional base, prevents the IFNL4 protein being expressed and the authors say it appears to have been selected for throughout evolution, becoming particularly common in Asian and European populations.

The authors say that the inhibition of IFNL4 could now present a future treatment strategy for HCV, as well as other diseases.

"By using RNA sequencing we looked outside the box to search for something beyond what was already known in this region ," said Ludmila Prokunina-Olsson, also from the National Cancer Institute. "We hit the jackpot with the discovery of a new gene."

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