Researchers Discover First Animal Strain of Hepatitis E Virus

The finding, published inthe Sept. 2, 1997 issue of the Proceedings of the National Academyof Sciences, should help advance studies of hepatitis E disease inhumans and eventually could lead to the development of a vaccine.

"This is a very interesting finding that will open new avenuesof research, and contribute to strategies to treat or prevent hepatitis Edisease," says Robert H. Purcell, M.D., chief of the hepatitis virusessection in NIAID's Laboratory of Infectious Diseases (LID) and seniorauthor of the study. "Unlike hepatitis A, B and C, hepatitis E diseasealmost never occurs in the United States. However, epidemics of thedisease do occur periodically in developing nations in Africa andAsia."

Hepatitis E virus is most commonly transmitted to peoplethrough 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 wherefatality 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 Stateshave occurred among travelers returning from areas where hepatitisE disease is endemic. Nevertheless, recent studies have shown thatupwards of 20 percent of healthy people in this country -- even thosewho have not traveled abroad -- have antibodies to hepatitis E virusor related agents in their blood. Similar evidence of exposure tohepatitis E virus or related agents also has been documented inprimates and swine.

To explore the nature of these infections in pigs, Xiang-JinMeng, M.D., Ph.D., working with Dr. Purcell and their LID colleagueSuzanne U. Emerson, Ph.D., screened swine blood samples with anassay designed to detect antibodies to strains of human hepatitis Evirus. Most of the samples, taken from swine herds in the MidwesternUnited States, tested positive for hepatitis E virus antibodies.

In a separate analysis, piglets born to antibody-negative sowswere 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 LIDscientists isolated putative hepatitis E virus genetic material fromswine blood samples and compared its genetic sequence to that ofhuman hepatitis E virus. They found that the swine virus was closelyrelated to, but distinct from, human strains of the virus.

"At the amino acid level, the swine and human strains areabout 90 percent alike," explains Dr. Meng. Amino acids are themolecules from which proteins are made. "Among most humanstrains of hepatitis E virus, amino acid identity is between 97 and 99percent." The researchers say their findings strongly suggest that apreviously unrecognized strain of hepatitis E virus circulates in theswine population.

"It's important to remember that the virus strain isolated fromthe swine in this study is distinct from the strains known to causedisease in humans," explains Dr. Meng. "Still, further studies areneeded to determine whether swine hepatitis E virus is species-specific or is circulating in the human population without causingdisease. These subclinical infections of humans with swine hepatitisE virus might explain the relatively high prevalence of hepatitis Eantibodies in healthy individuals in the United States."

If that were the case, says Dr. Meng, the strong immunologiccross-reactivity of the swine and human strains suggests that swinehepatitis E virus could prove useful as a vaccine against the humanvirus. The similarities between the swine and human viruses alsosuggest that pigs might provide an alternative animal model forstudying hepatitis E virus infection. Currently, scientists must useexpensive primate models to study the virus.

"The possibility that swine hepatitis E virus may infect humansalso raises a public health concern regarding the use of pig organs inhuman transplantation," cautions Dr. Purcell. "Nonpathogenic pigviruses could possibly become pathogenic in human transplantrecipients, particularly since transplant patients receive immune-suppressing drugs."

Apart from these concerns, Dr. Purcell adds, there is noevidence that the pig virus poses any threat to healthy humans orpigs.

"Swine hepatitis E virus is probably common throughout theworld," he says. "Antibodies to hepatitis E or related agents havebeen found in healthy swine as well as in several other species ofdomesticated and wild animals in a number of countries. Similarly,such antibodies have been found in most human populations, evenwhere hepatitis E disease does not occur. Furthermore, the degreeof genetic divergence of the swine virus from human hepatitis E virussuggests that it has been around for a long time."

In addition to the NIAID scientists, collaborators on this studyinclude Patrick G. Halbur, D.V.M., Ph.D., of the Iowa State UniversityCollege of Veterinary Medicine; Dale M. Webb, D.V.M., Ph.D., of theIllinois Department of Agriculture; James R. Lehman, D.V.M., ofAtlanta, Ill.; and other veterinarians in Iowa and Illinois.

NIAID, a component of the National Institutes of Health (NIH),supports research on AIDS, malaria and other infectious diseases, aswell as allergies and immunology. NIH and CDC are agencies of theU.S. Department of Health and Human Services. ###

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