Scientists at the National Institute of Allergy and Infectious Diseases (NIAID) in Bethesda, Md., have identified a strain of hepatitis E virus in pigs that is very similar to the strain that causes disease in humans. However, there is no evidence that the pig virus causes disease in either humans or pigs. The finding, published in the Sept. 2, 1997 issue of the Proceedings of the National Academy of Sciences, should help advance studies of hepatitis E disease in humans and eventually could lead to the development of a vaccine.
"This is a very interesting finding that will open new avenues of research, and contribute to strategies to treat or prevent hepatitis E disease," says Robert H. Purcell, M.D., chief of the hepatitis viruses section in NIAID’s Laboratory of Infectious Diseases (LID) and senior author of the study. "Unlike hepatitis A, B and C, hepatitis E disease almost never occurs in the United States. However, epidemics of the disease do occur periodically in developing nations in Africa and Asia."
Hepatitis E virus is most commonly transmitted to people through contaminated drinking water in areas with poor sanitation. The disease generally affects young adults and usually is not life-threatening, except in pregnant women infected with the virus where fatality rates of 15 to 20 percent have been reported.
According to the Centers for Disease Control and Prevention (CDC), virtually all cases of acute hepatitis E in the United States have occurred among travelers returning from areas where hepatitis E disease is endemic. Nevertheless, recent studies have shown that upwards of 20 percent of healthy people in this country -- even those who have not traveled abroad -- have antibodies to hepatitis E virus or related agents in their blood. Similar evidence of exposure to hepatitis E virus or related agents also has been documented in primates and swine.
To explore the nature of these infections in pigs, Xiang-Jin Meng, M.D., Ph.D., working with Dr. Purcell and their LID colleague Suzanne U. Emerson, Ph.D., screened swine blood samples with an assay designed to detect antibodies to strains of human hepatitis E virus. Most of the samples, taken from swine herds in the Midwestern United States, tested positive for hepatitis E virus antibodies.
In a separate analysis, piglets born to antibody-negative sows were found to seroconvert (develop antibodies to hepatitis E virus) when raised in large pens with other piglets. None of the piglets, however, showed any clinical signs of disease after seroconversion.
Using polymerase chain reaction (PCR) techniques, the LID scientists isolated putative hepatitis E virus genetic material from swine blood samples and compared its genetic sequence to that of human hepatitis E virus. They found that the swine virus was closely related to, but distinct from, human strains of the virus.
"At the amino acid level, the swine and human strains are about 90 percent alike," explains Dr. Meng. Amino acids are the molecules from which proteins are made. "Among most human strains of hepatitis E virus, amino acid identity is between 97 and 99 percent." The researchers say their findings strongly suggest that a previously unrecognized strain of hepatitis E virus circulates in the swine population.
"It’s important to remember that the virus strain isolated from the swine in this study is distinct from the strains known to cause disease in humans," explains Dr. Meng. "Still, further studies are needed to determine whether swine hepatitis E virus is species-specific or is circulating in the human population without causing disease. These subclinical infections of humans with swine hepatitis E virus might explain the relatively high prevalence of hepatitis E antibodies in healthy individuals in the United States."
If that were the case, says Dr. Meng, the strong immunologic cross-reactivity of the swine and human strains suggests that swine hepatitis E virus could prove useful as a vaccine against the human virus. The similarities between the swine and human viruses also suggest that pigs might provide an alternative animal model for studying hepatitis E virus infection. Currently, scientists must use expensive primate models to study the virus.
"The possibility that swine hepatitis E virus may infect humans also raises a public health concern regarding the use of pig organs in human transplantation," cautions Dr. Purcell. "Nonpathogenic pig viruses could possibly become pathogenic in human transplant recipients, particularly since transplant patients receive immune-suppressing drugs."
Apart from these concerns, Dr. Purcell adds, there is no evidence that the pig virus poses any threat to healthy humans or pigs.
"Swine hepatitis E virus is probably common throughout the world," he says. "Antibodies to hepatitis E or related agents have been found in healthy swine as well as in several other species of domesticated and wild animals in a number of countries. Similarly, such antibodies have been found in most human populations, even where hepatitis E disease does not occur. Furthermore, the degree of genetic divergence of the swine virus from human hepatitis E virus suggests that it has been around for a long time."
In addition to the NIAID scientists, collaborators on this study include Patrick G. Halbur, D.V.M., Ph.D., of the Iowa State University College of Veterinary Medicine; Dale M. Webb, D.V.M., Ph.D., of the Illinois Department of Agriculture; James R. Lehman, D.V.M., of Atlanta, Ill.; and other veterinarians in Iowa and Illinois.
Journal
Proceedings of the National Academy of Sciences