Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Investigators Discover New Gene That Affects Clearance of Hepatitis C Virus

11.01.2013
Scientists have discovered a gene that interferes with the clearance of hepatitis C virus infection.

They also identified an inherited variant within this gene, Interferon Lambda 4 (IFNL4), that predicts how people respond to treatment for hepatitis C infection. The results of this study, by investigators at the National Cancer Institute (NCI), part of the NIH, and their collaborators at NIH and other institutions, were published online in Nature Genetics on Jan. 6, 2013.


The novel protein, IFNL4—stained in red—as expressed in primary human liver cells treated to mimic the effect of infection with Hepatitis C (left). The protein shows up only in carriers of the unfavorable allele (right).

Chronic infection with hepatitis C virus is a cause of liver cirrhosis and liver cancer. Up to 80 percent of people who are acutely infected with hepatitis C fail to clear the virus and develop chronic hepatitis C infection, and of these, approximately 5 percent develop liver cancer. Individuals of African ancestry do not respond as well to current treatments of hepatitis C infection compared to patients of European or Asian ancestry.

Previously, results from genome-wide association studies (GWAS) identified common inherited genetic markers that were associated with response to hepatitis C virus treatment and spontaneous clearance of the infection. Those markers are located on chromosome 19 near a known interferon gene, IFNL3 (IL28B). However, molecular investigations into IFNL3 did not explain the GWAS association with spontaneous virus clearance or treatment response. To find the new gene, the investigators used a technology involving RNA sequencing on human liver cells treated to mimic hepatitis C virus infection.

“By using RNA sequencing we looked outside the box to search for something beyond what was already known in this region. We hit the jackpot with the discovery of a new gene. It is possible that other important genes may be discovered using this approach,” said co-lead investigator Ludmila Prokunina-Olsson, Ph.D., of the Laboratory of Translational Genomics in NCI’s Division of Cancer Epidemiology and Genetics (DCEG).

The researchers found that the IFNL4 region harbors a variant that is found in two alternative forms. One form, called deltaG, results in a deletion in one of the four bases that comprise DNA. The change creates an alteration known as a frameshift, which produces the IFNL4 protein, while the form without the deletion does not produce IFNL4. By analyzing data from hepatitis C-infected African-Americans and European-Americans participating in clinical studies, the authors found that the presence of the IFNL4 protein is associated with poorer clearance and response to treatment than the form that does not produce IFNL4. The deletion variant is more common in people of African ancestry, which helps partially explain why African-Americans have a lower response to current hepatitis C treatments than patients of Asian and European ancestry.

“Our work fulfills several promises of the genomic era,” said NCI’s Thomas R. O’Brien, M.D., Infections and Immunoepidemiology Branch, DCEG. “One, a better understanding of biology; two, personalized medicine; and three, new potential treatments. We deliver immediately on the first two. 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. For the third, the INFL4 protein may be used as a novel therapeutic target for hepatitis C virus infection, and possibly other diseases.”

The new gene belongs to what is now a family of four interferon-lambda protein-encoding genes, three of which were discovered more than ten years ago (IFNL1, IFNL2 and IFNL3) The mechanism by which the IFNL 4 protein impairs hepatitis C virus clearance remains unknown. Further studies will explore molecular function of this novel protein in normal and disease conditions.

This study was conducted collaboratively with the National Institute of Diabetes and Digestive and Kidney Diseases at NIH, as well as the U.S. Food and Drug Administration, and a number of universities and research institutions. Funding was provided by NCI grant Z01 CP005782.

NCI Press Officers | Newswise
Further information:
http://www.nih.gov

More articles from Life Sciences:

nachricht 'Y' a protein unicorn might matter in glaucoma
23.10.2017 | Georgia Institute of Technology

nachricht Microfluidics probe 'cholesterol' of the oil industry
23.10.2017 | Rice University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Salmonella as a tumour medication

HZI researchers developed a bacterial strain that can be used in cancer therapy

Salmonellae are dangerous pathogens that enter the body via contaminated food and can cause severe infections. But these bacteria are also known to target...

Im Focus: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

3rd Symposium on Driving Simulation

23.10.2017 | Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

 
Latest News

Microfluidics probe 'cholesterol' of the oil industry

23.10.2017 | Life Sciences

Gamma rays will reach beyond the limits of light

23.10.2017 | Physics and Astronomy

The end of pneumonia? New vaccine offers hope

23.10.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>