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Hepatitis C Virus Mutates to Escape Human Immune System
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Accession Number
A00136
Author
National Institutes of Health (NIH), National Institute of Allergy and Infectious Diseases (NIAID)
Source
NIAID News
Release Date
August 1, 1994
Major Descriptors
Hepatitis C virus (HCV)
Topic
Hepatitis
Text
The human immune system can neutralize the liver-damaging hepatitis C virus (HCV), but the virus evades this protective defense by rapidly mutating and then causes disease, according to a study by researchers from the National Institutes of Health (NIH), Georgetown University and Bioqual, Inc. The study appears in the Aug. 2 "Proceedings of the National Academy of Sciences."
The findings raise concerns for the development of a broadly reactive vaccine against HCV," says lead author Patrizia Farci, M.D., a visiting scientist in the Laboratory of Infectious Diseases (LID) at the National Institute of Allergy and Infectious Dieases (NIAID), part of NIH. "The study provides evidence that HCV infection elicits a neutralizing antibody response in humans, but the antibodies are isolate specific. A successful vaccine must protect against multiple HCV isolates. The high degree of genetic differences among HCV strains may represent an obstacle to the development of an effective vaccine."
Up to 5 million people worldwide are infected with HCV, at least half of whom will develop chronic liver inflammation. Up to 20 percent will develop cirrhosis, which frequently leads to liver cancer. HCV is one of five hepatitis viruses known to cause liver disease: A, B, C, Delta (D), and E. HCV can be spread via contaminated blood transfusions, sharing needles with infected individuals and possibly by other means such as sexual intercourse.
In the study, investigators successfully blocked HCV infection in chimpanzees who received a mixture of the strain of HCV found in a patient during the acute-phase of hepatitis, caused by a contaminated blood transfusion in 1977, and neutralizing antibodies from the same chronically HCV-infected patient two years later.
In contrast, plasma from the same patient in 1990 could not neutralize HCV when scientist inoculated two other chimpanzees with the mixture.
Using genetic sequencing tests, the scientists determined that HCV strains recovered in the patient's plasma from 1979 and 1990 had mutated from the 1977 strain. In fact, the patient's 1977 and 1990 strains of HCV differed in one section of their genetic sequences by more than 28 percent. In addition, genetic analysis revealed that the virus strains from the chimpanzees were different from the principal strain used for inoculation.
The HCV strain recovered from the patient's plasma in 1979 had a striking similarity to the strain recovered from one of the infected chimpanzees inoculated with the 1977 strain," says Robert H. Purcell, M.D., chief of Hepatitis Virus Section in LID. "This genetic correspondence suggests that the predecessor of the new strain was present in the patient in 1977."
This evidence," he continues, "together with the different sequences of HCV recovered from the chimpanzees that received the same virus strain, confirms that HCV is present in the body as a mix of several strains."
Drs. Farci and Purcell's coauthors include Doris C. Wong,B.A., and Roger H. Miller, Ph.D., of NIAID, Harvey J. Alter, M.D., of the Department of Transfusion Medicine of the Warren G. Magnuson Clinical Center at NIH, Sugantha Govindarajan, M.D., of the Rancho Los Amigos Hospital in Downey, Calif., Ronald Engle, B.S., of the Department of Microbiology at Georgetown University in Washington, D.C., and Max Shapiro, A.S., of Bioqual, Inc. of Rockville, MD.
As part of NIH, NIAID supports investigators and scientific studies at universities, medical schools, hospitals and research institutions in the United States and abroad aimed at preventing, diagnosing and treating such illnesses as AIDS, tuberculosis and asthma as well as allergies. NIH is an agency of the U.S. Public Health Service, part of the U.S. Department of Health and Human Services.
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