Hepatitis A Immune Response Has Implications for Hepatitis C

[Guest guest]

http://www.hivandhepatitis.com/hep_c/news/2011/0708_2011_c.html

Hepatitis A Immune Response Has Implications for Hepatitis C

SUMMARY

Hepatitis A virus appears to evade immune defenses better than hepatitis C

virus, even though it only causes short-term illness. Learning about differences

between viral dynamics and immune response to HAV and HCV may offer information

that can inform treatment.

Hepatitis A virus (HAV) is a picornavirus that causes only acute infection, as

the immune system can clear the virus its own without treatment. Hepatitis C

virus (HCV), in contrast, is a flavivirus that often causes chronic infection.

The main similarity is that the 2 viruses both target the liver.

As described in the July 5, 2011, Proceedings of the National Academy of

Sciences USA, Lanford from the Texas Biomedical Research Institute and

colleagues compared viral activity and immune response to HAV and HCV in

chimpanzees.

Below is an edited excerpt from a press release issued by the Southwest

Foundation for Biomedical Research describing the study and its findings.

New Study Reveals How the Immune System

Responds to Hepatitis A Virus

Has implications for future of hepatitis C research

June 20, 2011 -- A surprising finding in a study comparing hepatitis C virus

(HCV) with hepatitis A virus (HAV) infections in chimpanzees by a team that

includes scientists from the Texas Biomedical Research Institute sheds new light

on the nature of the body's immune response to these viruses.

Understanding how hepatitis C becomes chronic is very important because some 200

million people worldwide and 3.2 million people in the U.S. are chronically

infected with HCV and are at risk for progression to cirrhosis and liver cancer.

Hepatitis C associated liver disease is the most common indication for liver

transplantation, while liver cancer due to HCV infection is now the most rapidly

increasing cause of cancer death in the U.S.

" Remarkably, we found that HAV was more adept at evading the innate immune

response than HCV, the virus that ultimately causes chronic infections, " said

E. Lanford, PhD, a Texas Biomed virologist. The novel findings

demonstrate that HAV is the stealthier virus when it comes to evading the innate

immune response, despite the lack of persistent infections.

Hepatitis C infections are characterized by a failure of the immune system to

combat and eliminate the virus. " We suspect this failure of the immune system

shares attributes with other persistent viruses such as HIV and hepatitis B

virus, " said Lanford. By comparing two similar viruses that infect the liver,

one that is always cleared by the immune system, HAV, and one that frequently

evades the immune response, HCV, the team hoped to unravel the mystery of how

HCV causes lifelong persistent infections.

The research team involved scientists from Texas Biomed in San , the

University of North Carolina (UNC) at Chapel Hill, and Nationwide Children's

Hospital in Columbus, Ohio. The study performed in chimpanzees at Texas Biomed's

Southwest National Primate Research Center (SNPRC) and funded by the National

Institutes of Health, is published today in Proceedings of the National Academy

of Sciences U.S.A.

The new study points out the critical need for more information about how the

immune system reacts to HCV. It also reinforces the importance of chimpanzee

research in this effort. The chimpanzee, the only animal model susceptible to

HCV infection, was critical for probing the molecular differences in gene

expression in the liver related to infection by the two viruses.

Examination of the adaptive immune system by co-author M. ,

PhD, of Nationwide Children's Hospital in Columbus, Ohio, found that the T cell

response to HAV was unique as well. " We expected the immune response to kill all

HAV infected cells in a short time frame, and yet we could detect the genome of

the virus in the liver for up to one year, long after symptoms of the disease

were resolved, " Lanford explained.

" Hepatitis viruses have co-evolved with humans over a very long period of time

and they are good at evading the immune system, but nobody understands how

hepatitis C becomes a chronic infection, " said co-author Stanley M. Lemon, MD,

of UNC.

" The surprising and exciting results of this research program further highlight

the critical value of the chimpanzee model in research on hepatitis, " said

L. VandeBerg, PhD, Texas Biomed's chief scientific officer and SNPRC director.

Investigator affiliations: Department of Virology and Immunology, Texas

Biomedical Research Institute, and Southwest National Primate Research Center,

San , TX; Division of Infectious Diseases, Department of Medicine, Center

for Translational Immunology, and the Lineberger Comprehensive Cancer Center,

University of North Carolina, Chapel Hill, NC; Center for Vaccines and Immunity,

Research Institute at Nationwide Children's Hospital, Columbus, OH; Theoretical

Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM.

7/8/11

Reference

RE Lanford, Z Feng, D Chavez, et al. Acute hepatitis A virus infection is

associated with a limited type I interferon response and persistence of

intrahepatic viral RNA. Proceedings of the National Academy of Sciences USA

108(27):11223-11228 (abstract). July 5, 2011.

Other Sources

Southwest Foundation for Biomedical Research. New Study Reveals How the Immune

System Responds to Hepatitis A Virus. Press release. June 20, 2011.

University of North Carolina School of Medicine. Acute Hepatitis A Evades Immune

System More Effectively than Chronic Cousin. Press release. June 20, 2011.