HCV changes its surface proteins as soon as antibodies begin to
attack it; in essence, the virus slips into a disguise and
continues on without detection Scientists from the National
Institutes of Health (NIH) and other institutions have discovered a
clue that begins to explain why so many patients fail to fully
recover from infection with the hepatitis C virus (HCV). Their
research, reported in the current issue of Science, points to
changes in surface proteins that enable the virus to evade the
immune system. The study shows that the ultimate outcome of an HCV
infection is determined during the initial, acute phase of disease.
"Hepatitis C is a devastating disease that exacts a significant
toll in this country and abroad, and whose full clinical impact has
yet to be realized," states Anthony S. Fauci, MD, director of the
National Institute of Allergy and Infectious Diseases (NIAID) at
the NIH. "This research helps to explain how the virus manages to
persist in the body and provides physicians with a potential way to
predict the development of a chronic infection."
Nearly 4 million Americans have been infected with the hepatitis
C virus (HCV). Of those who contract hepatitis C, 85 percent remain
chronically infected, harboring a virus that continues to replicate
throughout a person's life. HCV is a major cause of chronic liver
disease and is responsible for a third of all cases of cirrhosis
and liver cancer, half of all liver transplants, and 8,000 to
10,000 deaths in this country annually.
Patrizia Farci, MD, and Robert Purcell, MD, of NIAID and Harvey
Alter, MD, of the NIH Warren Magnuson Clinical Center, led a team
of scientists in a study designed to see whether the hepatitis C
virus changes during infection. Dr. Alter had been conducting
long-term studies of patients who contracted hepatitis from blood
transfusions. These individuals subsequently developed different
clinical outcomes, ranging from short-term infections to chronic
disease. Some of these patients have had hepatitis C for over 20
years. "This unique group was critical for our study, because they
had been observed continuously since early in infection," states
Dr. Farci, who splits her time between NIAID in the United States
and the University of Cagliari in Italy.
Three of the 12 patients studied had acute HCV infections, three
had fulminant hepatitis (a rare but serious form of acute disease),
and six had chronic hepatitis. The research team examined the virus
in each person, looking specifically for changes in the genes that
encode special proteins coating the viral surface. They also
studied what changes occurred either before or after the body's
immune system responded to HCV infection.
In some patients, the virus remained relatively unchanged
following the initial immune response, and those people completely
eliminated HCV over several weeks. In most, however, genetic HCV
variants began to appear in response to the early immune assault.
This rapid viral evolution ultimately resulted in chronic
infection.
"We know that the body responds to infection early in the
disease process, but in most patients the virus is 'smarter' than
the immune system," states Dr. Farci. "In many cases, HCV changes
its surface proteins as soon as the patient's antibodies begin to
attack. In essence, the virus slips into a disguise and continues
on without detection."
Similar masquerades are used by other viruses, such as HIV and
influenza, but this is the first study to correlate such behavior
with disease progression in hepatitis C. The researchers also
determined a region on virus surface proteins where most of the
changes occur. Their studies will now focus on the types of
mutations that assist HCV in avoiding the immune system, and on the
types of antibodies produced during the early response. By
understanding more about this critical checkpoint in HCV infection,
they hope to develop new tools for hepatitis C treatment and
prevention.
Other collaborators from NIH, University of Cagliari, Kanazawa
University (Japan), Chiron Corporation, and Albert Einstein Medical
Center participated in this study.
4/13/00
Reference:
P Farci and others. The outcome of acute hepatitis C predicted by
the evolution of the viral quasispecies. Science 288:339-44
(2000).
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