Researchers from the National Institutes of Health have recovered a virus similar to the hepatitis E virus (HEV) from rats in Los Angeles, California, a finding that may explain high levels of HEV exposure in inner-city residents without disease. They report their findings today at the 50th Annual Meeting of the American Society of Tropical Medicine and Hygiene.
"There is a fair amount of antibodies to HEV in humans in the United States, suggesting exposure, but very little clinical manifestations of the disease," says Robert Purcell, Co-Chief of the Laboratory of Infectious Diseases and Head of the Hepatitis Viruses Section of the National Institute of Allergy and Infectious Disease and primary author of the study.
HEV infection is one of the most common causes of hepatitis in central Asia. Unlike some other forms of hepatitis, like hepatitis B and C, HEV infection is self-limiting, lasting 1 to 4 weeks, and is generally not life threatening, except in pregnant women where fatality rates of 15 to 20 percent have been reported.
According to the Centers for Disease Control and Prevention, most cases of HEV disease in the United States have occurred among travelers returning from developing countries. Still, between 1 and 5 percent of healthy blood donors in the United States have HEV antibodies in their blood with rates over 20 percent in some inner city areas.
Swine have been shown to be a possible source of HEV exposure and the swine virus, while quite similar to the human virus, does not appear to cause disease, at least in swine.
"However, most inner-city residents do not come into contact with pigs on a regular basis," says Purcell. "That was when we got interested in looking at rats." Previous studies have shown that a high percentage of wild rats in the United States have antibodies against HEV, suggesting previous infection. While pigs are not ubiquitous in urban areas, rats are. Because HEV infections are relatively short-lived, though, recovering the virus from rats can be very tricky.
"What we did in this study was try to recover the agent from wild rats. You have to be lucky to find a rat that is acutely infected," says Purcell.
To increase their odds, Purcell and his colleagues examined only rats that did not have antibodies to HEV, hoping that there would be a chance that those rats were incubating the virus. They also included rats that tested negative for long-term antibodies against the virus (that would appear after infection) but tested positive for shorter-term antibodies (the type that would appear during acute infection).
They tested 80 rats from Los Angeles County and Orange County in California, Baltimore and Hawaii, extracting sera and injecting it into laboratory rats. Three of the laboratory rats that had been inoculated with sera from rats in Los Angeles developed disease.
Purcell warns that they have only recovered the virus and have yet to isolate and characterize it. "HEV doesn't grow in laboratory cell cultures. So far we've only recovered the rat agent from wild rats and have transmitted it to laboratory rats, so we know there's a transmissible agent there and it is serologically related to HEV," he says. He does believe the virus may end up being significantly different from human and swine HEV as the primers used to amplify RNA of those viruses do not work on this new agent.
It is possible that these infected rats may contribute to the the high rates of humans with HEV antibodies in inner cities, says Purcell, but more tests need to be done. For the next step they must develop a specific antibody diagnostic for the rat virus and test humans with it to see if they have been infected by the rat virus.
Exposure does have its upside. Having antibodies to HEV, regardless of the source, appears to protect against future disease. In a related study, Purcell will also present information on the results of an experimental vaccine against HEV. It has been tested in primates with promising results and is currently in human trials.
The results in humans could be available as early as next year.
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