Featured Research

from universities, journals, and other organizations

Key To Hepatitis Virus Persistence Found

Date:
April 18, 2003
Source:
NIH/National Institute Of Allergy And Infectious Diseases
Summary:
Scientists at two Texas universities have discovered how hepatitis C virus thwarts immune system efforts to eliminate it. The finding, published online today in ScienceExpress, could lead to more effective treatments for liver disease caused by hepatitis C virus.

Scientists at two Texas universities have discovered how hepatitis C virus thwarts immune system efforts to eliminate it. The finding, published online today in ScienceExpress, could lead to more effective treatments for liver disease caused by hepatitis C virus, says author Michael Gale, Jr., Ph.D., of University of Texas Southwestern Medical Center at Dallas. Dr. Gale and coauthor Stanley Lemon, M.D., of University of Texas Medical Branch at Galveston, are grantees of the National Institute of Allergy and Infectious Diseases (NIAID).

"Persistent hepatitis C virus (HCV) infection is a major cause of liver disease worldwide and is the leading reason for liver transplants in this country," notes NIAID Director Anthony S. Fauci, M.D. "The most prevalent form of HCV in the United States is, unfortunately, the least responsive to available treatments. Moreover, African Americans are even less responsive to therapy than Caucasians," he adds.

The immune system has many ways to detect and fight off invading microbes, and microbes have just as many ways to elude and disarm immune system components. Through a series of experiments on cells grown in the laboratory, Drs. Gale and Lemon defined the strategy HCV uses to evade the host's immune response. As HCV begins to replicate in its human host, it manufactures enzymes, called proteases, which it requires to transform viral proteins into their functional forms. The Texas investigators determined that one viral protease, NS3/4A, specifically inhibits a key immune system molecule, interferon regulatory factor-3 (IRF-3). IRF-3 orchestrates a range of antiviral responses. Without this master switch, antiviral responses never begin, and HCV can gain a foothold and persist in its host.

Next, the scientists searched for ways to reverse the IRF-3 blockade. They applied a protease inhibitor to human cells containing modified HCV. This prevented the virus from making functional NS3/4A and restored the cells' IRF-3 pathway. Follow-up studies have shown that once restored, the immune response reduced viral levels to nearly undetectable levels within days, according to Dr. Gale.

The identification of this viral protease-regulated control of IRF-3 opens new avenues in both clinical and basic research on hepatitis C, notes Dr. Gale. Until now, scientists had not considered the possibility that inhibiting this protease did anything more than halt viral replication. "Now that we know NS3/4A inhibition essentially restores the host's immune response to the virus, we can assess hepatitis drug candidates for this ability as well," Dr. Gale says.

NS3/4A will be a valuable tool in further dissecting the roles of viral proteases and their host cell targets, says Dr. Gale. For example, the scientists plan to use NS3/4A to hunt for the still unknown host cell enzyme responsible for activating IRF-3. Conceivably, Dr. Gale explains, future therapeutic approaches to viral disease could involve boosting the activity of any key host enzymes that are found.

"Understanding the tricks that the hepatitis C virus employs to impair the immune system represents an important advance with potential implications for successful cure of those suffering from liver disease," says Leslye Johnson, Ph.D., chief of NIAID's enteric and hepatic diseases branch.

###NIAID is a component of the National Institutes of Health (NIH), which is an agency of the Department of Health and Human Services. NIAID supports basic and applied research to prevent, diagnose, and treat infectious and immune-mediated illnesses, including HIV/AIDS and other sexually transmitted diseases, illness from potential agents of bioterrorism, tuberculosis, malaria, autoimmune disorders, asthma and allergies.

Reference: E, et al. Regulation of interferon regulatory factor-3 by the hepatitis C virus serine protease. Science, April 17, 2003. DOI 10.1126/science.1082604.


Story Source:

The above story is based on materials provided by NIH/National Institute Of Allergy And Infectious Diseases. Note: Materials may be edited for content and length.


Cite This Page:

NIH/National Institute Of Allergy And Infectious Diseases. "Key To Hepatitis Virus Persistence Found." ScienceDaily. ScienceDaily, 18 April 2003. <www.sciencedaily.com/releases/2003/04/030418081413.htm>.
NIH/National Institute Of Allergy And Infectious Diseases. (2003, April 18). Key To Hepatitis Virus Persistence Found. ScienceDaily. Retrieved August 21, 2014 from www.sciencedaily.com/releases/2003/04/030418081413.htm
NIH/National Institute Of Allergy And Infectious Diseases. "Key To Hepatitis Virus Persistence Found." ScienceDaily. www.sciencedaily.com/releases/2003/04/030418081413.htm (accessed August 21, 2014).

Share This




More Health & Medicine News

Thursday, August 21, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Drug Used To Treat 'Ebola's Cousin' Shows Promise

Drug Used To Treat 'Ebola's Cousin' Shows Promise

Newsy (Aug. 21, 2014) An experimental drug used to treat Marburg virus in rhesus monkeys could give new insight into a similar treatment for Ebola. Video provided by Newsy
Powered by NewsLook.com
Cadavers, a Teen, and a Medical School Dream

Cadavers, a Teen, and a Medical School Dream

AP (Aug. 21, 2014) Contains graphic content. He's only 17. But Johntrell Bowles has wanted to be a doctor from a young age, despite the odds against him. He was recently the youngest participant in a cadaver program at the Indiana University NW medical school. (Aug. 21) Video provided by AP
Powered by NewsLook.com
Possible Ebola Patient in Isolation at California Hospital

Possible Ebola Patient in Isolation at California Hospital

Reuters - US Online Video (Aug. 20, 2014) A patient who may have been exposed to the Ebola virus is in isolation at the Kaiser Permanente South Sacramento Medical Center. Linda So reports. Video provided by Reuters
Powered by NewsLook.com
Reasons Why Teen Birth Rates Are At An All-Time Low

Reasons Why Teen Birth Rates Are At An All-Time Low

Newsy (Aug. 20, 2014) A CDC report says birth rates among teenagers have been declining for decades, reaching a new low in 2013. We look at several popular explanations. Video provided by Newsy
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:
from the past week

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