A Immune Response Has Implications for Hepatitis C
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.
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.
described in the July
5, 2011, Proceedings of the National Academy of Sciences USA,
Robert 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.
Study Reveals How the Immune System
Responds to Hepatitis A Virus
implications for future of hepatitis C research
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 Robert 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
Antonio, 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 Christopher
M. Walker, 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 John 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 Antonio, 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,
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.
Foundation for Biomedical Research. New Study Reveals How the
Immune System Responds to Hepatitis A Virus. Press release. June
of North Carolina School of Medicine. Acute Hepatitis A Evades
Immune System More Effectively than Chronic Cousin. Press release.
June 20, 2011.