Danger signal limits Hepatitis C infection

Despite the fact that hepatitis C virus (HCV) persists chronically in about 80 percent of those infected, some liver cells remain free of the virus even after many years. Now Sung Key Jang of Pohang University of Science and Technology, South Korea, et al. explain that paradox. During chronic HCV infection, a cellular protein, HMGB1, helps restrain viral reproduction. That prevents HCV from sweeping the liver, and results in a lower blood burden of virus than in the case of hepatitis B. This first description of HMGB1-related responses triggered by HCV infection is published in the September 2011 issue of the Journal of Virology.

The researchers show further that HCV-infected cells secrete HMGB1 proteins into the extracellular milieu. There, these proteins trigger a receptor on the cytoplasmic membrane, called TLR4, causing both an interferon response, which fights the virus, and an inflammatory response.
 
Two different responses coming from the same receptor at the same time is a common phenomenon. But that can make designing drugs all the more complicated. Boosting the interferon response could vanquish the virus, but the inflammatory response would be harmful. However, Jang says that it might be possible to get the one response without the other. If HMGB1 in the TLR4 receptor is like a hand that fits nicely in a glove, thus triggering both responses, perhaps a drug could be fashioned which could fit a piece of the receptor, like two fingers in a glove, thus triggering only the interferon response. This is an unpublished hypothesis, says Jang, but one that his group is working on.
 
In the paper, the researchers note that HMGB1 is a “danger” signal. The Danger model of immunology, derived by Polly Matzinger of the National Institute of Allergy and Infectious Disease, NIH, posits that immune responses are initiated by signals from damaged cells. Rather than distinguishing between “self” and “nonself,” as per conventional wisdom, the Danger model suggests that when cells are stressed, injured, or killed (by external forces rather than through so-called programmed cell death), they give off alarm signals that activate the immune system to clear the damaging agents.
www.direct-ms.org/pdf/Immunolo… eral/DangerModel.pdf
 
About 18 million people worldwide are infected with HCV. That virus causes inflammation (hepatitis), massive death of (cirrhosis), and hepatocellular carcinoma. Liver cancer, primarily hepatocellular carcinoma, which is also caused by heptatitis B virus, is the third leading cause of cancer deaths worldwide, and the ninth leading cause of cancer deaths in the United States, according to Morbidity and Mortality Weekly Report http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5917a3.htm/ .

More information: J. Ha Jung, et al., 2011. Hepatitis C virus infection is blocked by HMGB1 released from virus-infected cells. J. Virol. 85:9359-9368

American Society for Microbiology

not rated yet
add to favorites email to friend print save as pdf

Related Stories

Keeping hepatitis C virus at bay after a liver transplant

Oct 01, 2009

One of the most common reasons for needing a liver transplant is liver failure or liver cancer caused by liver cell infection with hepatitis C virus (HCV). However, in nearly all patients the new liver becomes infected with ...

Improved culture system for hepatitis C virus infection

Jul 16, 2008

A University of California, San Diego School of Medicine researcher has developed the first tissue culture of normal, human liver cells that can model infection with the Hepatitis C virus (HCV) and provide a realistic environment ...

Early treatment is key to combating hepatitis C virus

Aug 08, 2008

Canadian researchers have shown that patients who receive early treatment for Hepatitis C virus (HCV) within the first months following an infection, develop a rapid poly-functional immune response against HCV similar to ...

Pinpointing a tell-tale mark of liver cancer

Jul 08, 2011

Persistent hepatitis C virus (HCV) infection can lead to chronic hepatitis C and then progress to fatal liver diseases including liver cirrhosis and liver cancer, the third most common cause of cancer-related ...

New vaccine for hepatitis C virus

Jul 28, 2011

Murdoch University researchers have begun a study to develop a new and innovative vaccine for the hepatitis C virus (HCV).

Recommended for you

Ebola isolation at US base 'pretty much vacation'

5 hours ago

With plenty of flat screen TVs, game nights and even an outdoor fire pit, life in isolation for members of the U.S. military who have returned from the Ebola mission in West Africa can look a lot like summer camp.

Chinese-built Ebola center dedicated in Liberia

8 hours ago

China, one of the first countries to send aid to battle Ebola in West Africa, ramped up the assistance significantly Tuesday by opening a 100-bed treatment center in Liberia as rows of uniformed Chinese army ...

User comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.