Featured Research

from universities, journals, and other organizations

Newly found tactics in offense-defense struggle with hepatitis C virus

Date:
February 10, 2014
Source:
University of Washington
Summary:
The hepatitis C virus (HCV) has a previously unrecognized tactic to outwit antiviral responses and sustain a long-term infection. It also turns out that some people are genetically equipped with a strong countermeasure to the virus' attempt to weaken the attack on it. The details of these findings suggest potential targets for treating HCV.

The hepatitis C virus (HCV) has a previously unrecognized tactic to outwit antiviral responses and sustain a long-term infection. It also turns out that some people are genetically equipped with a strong countermeasure to the virus' attempt to weaken the attack on it.

Related Articles


The details of these findings suggest potential targets for treating HCV, according to a research team led by Dr. Ram Savan, assistant professor of immunology at the University of Washington. The study was published in Nature Immunology.

HCV infects more than 150 million of the world's people. The virus is notorious for evading the body's immune system and establishing an infection that can continue for decades, despite treatment. A lasting infection can damage the liver, and in some cases produce liver cancer. HCV infection is a major cause of liver failure requiring an organ transplant.

The virus, hiding in other tissues, can return in the transplanted liver. HCV and the human immune system are engaged in a seemingly never-ending duel, each trying to overcome the others latest move. Several HCV mechanisms for defying the body's immune system have already been uncovered.

Present treatments are about 70 percent effective in curing the infection, Savan said. The triple combination treatments consist of interferon, ribavirin and direct-acting antiviral agents.

He added, however, that resistant strains of HCV are emerging in antiviral treated patients. Also troubling, he said, is that certain patients can undergo almost a year of treatment weeks -- and still be infected. They've endured the unpleasant, flu-like side effects of the regimen with little benefit.

After observing that patients of Asian descent reacted better to HCV treatment than did those of African descent, other research teams searched entire human genomes to identify gene clusters associated with response to therapy.

On chromosome 19, the scientists found different, single-letter DNA code changes linked to treatment response and the natural ability to clear HCV infection.

These tiny genetic variations are located near an area that encodes for interferon-lamda3 (IFNL3), also called interleukin-28B. Viruses can trigger blood cells and other cells to produce this potent substance, which is released to protect against virus invasion.

The mechanism aligning this genetic finding with clearance of HCV had been elusive, Savan's group noted in their paper. His team discovered how the single-letter variation in the IFNL3 gene was responsible for the differences between those who could and those who could not effectively clear HCV.

Individuals who carry the T (for thymidine) variant have an unfavorable outcome in fighting HCV, while those who carry the G (for guanosine) variant have a favorable outcome.

Their data showed that HCV could induce liver cells to target the activities of the IFNL3 gene with two microRNAs. MicroRNAs are silencers: They stop the messengers who transmit information to produce a protein from a gene, in this case the production of the antiviral interferon lambda-3.

These two particular microRNAs are generally turned off in liver cells, until HCV coerces them to act on its behalf. Normally, these so called myomiRs are associated with myosin-encoding genes in skeletal and heart muscle.

"This is a previously unknown strategy by which HCV evades the immune system and suggests that these microRNAs could be therapeutic targets for restoring the host antiviral response," the researchers wrote in their paper. Adding support to this suggestion is the researchers' observation that the bad-acting microRNAs in question could not land on and repress interferon lambda-3, if the host carried the favorable "G" variant.

In those cases, the host is able to escape adverse regulation by HCV, the researchers observed. Savan pointed out that this particular escape variant has been found only in humans, and not in other primates. He said it is not yet known if the G variant arose in humans as a response to selective pressure by infection with HCV.


Story Source:

The above story is based on materials provided by University of Washington. Note: Materials may be edited for content and length.


Journal Reference:

  1. Adelle P McFarland, Stacy M Horner, Abigail Jarret, Rochelle C Joslyn, Eckart Bindewald, Bruce A Shapiro, Don A Delker, Curt H Hagedorn, Mary Carrington, Michael Gale, Ram Savan. The favorable IFNL3 genotype escapes mRNA decay mediated by AU-rich elements and hepatitis C virus–induced microRNAs. Nature Immunology, 2013; 15 (1): 72 DOI: 10.1038/ni.2758

Cite This Page:

University of Washington. "Newly found tactics in offense-defense struggle with hepatitis C virus." ScienceDaily. ScienceDaily, 10 February 2014. <www.sciencedaily.com/releases/2014/02/140210095412.htm>.
University of Washington. (2014, February 10). Newly found tactics in offense-defense struggle with hepatitis C virus. ScienceDaily. Retrieved December 19, 2014 from www.sciencedaily.com/releases/2014/02/140210095412.htm
University of Washington. "Newly found tactics in offense-defense struggle with hepatitis C virus." ScienceDaily. www.sciencedaily.com/releases/2014/02/140210095412.htm (accessed December 19, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Friday, December 19, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

The Best Tips to Curb Holiday Carbs

The Best Tips to Curb Holiday Carbs

Buzz60 (Dec. 19, 2014) It's hard to resist those delicious but fattening carbs we all crave during the winter months, but there are some ways to stay satisfied without consuming the extra calories. Vanessa Freeman (@VanessaFreeTV) has the details. Video provided by Buzz60
Powered by NewsLook.com
Sierra Leone Bikers Spread the Message to Fight Ebola

Sierra Leone Bikers Spread the Message to Fight Ebola

AFP (Dec. 19, 2014) More than 100 motorcyclists hit the road to spread awareness messages about Ebola. Nearly 7,000 people have now died from the virus, almost all of them in west Africa, according to the World Health Organization. Video provided by AFP
Powered by NewsLook.com
Researchers Test Colombian Village With High Alzheimer's Rates

Researchers Test Colombian Village With High Alzheimer's Rates

AFP (Dec. 19, 2014) In Yarumal, a village in N. Colombia, Alzheimer's has ravaged a disproportionately large number of families. A genetic "curse" that may pave the way for research on how to treat the disease that claims a new victim every four seconds. Duration: 02:42 Video provided by AFP
Powered by NewsLook.com
Double-Amputee Becomes First To Move Two Prosthetic Arms With His Mind

Double-Amputee Becomes First To Move Two Prosthetic Arms With His Mind

Buzz60 (Dec. 19, 2014) A double-amputee makes history by becoming the first person to wear and operate two prosthetic arms using only his mind. Jen Markham has the story. Video provided by Buzz60
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins