A study on these findings was published Wednesday in the online edition of the Journal of Medical Virology, by scientists from Oregon State University, the Center for Pediatric Research at Eastern Virginia Medical School, and AVI BioPharma.
The association between viral infection and the presence of a disease of unknown cause does not prove cause and effect, the researchers say, but the data are intriguing and raise important new questions. Further research is needed to establish proof that infection with this virus in humans is causing liver damage or some other problems, which may include encephalitis and spontaneous abortion.
The viral group being studied is the genus Vesivirus, one of four genera in the Caliciviridae viral family. Some caliciviruses cause disease in humans, such as the Norwalk virus that causes gastroenteritis. Other caliciviruses cause a wide range of disease in other animal species. The Lagovirus genus causes a fatal hemorrhagic disease and hepatitis that has killed millions of rabbits across four continents in the past 20 years.
In more than 30 years of research, part of what has been found to be unusual about caliciviruses is that they can cause multiple diseases and affect a broad range of marine and terrestrial animal species - a single Vesivirus serotype has infected species as diverse as fish, seals, shellfish, swine, cattle, primates and humans, the researchers said in their report.
In the latest study on potential human impacts, scientists looked at samples from more than 700 blood donors at a laboratory that serves eight western states, as well as some samples from patients with clinical hepatitis.
In four study groups, the researchers found:
- In blood samples from normal blood donors that had been determined to be safe and were used in blood transfusions, 12 percent showed antibody to Vesivirus, suggesting a previous infection.
- In donors who had evidence of liver damage based upon a liver enzyme test, and whose blood had been discarded as a result, 21 percent had antibodies to Vesivirus.
- In blood samples from persons who had been diagnosed with clinical hepatitis, 29 percent had antibodies to Vesivirus.
- In persons who previously had transfusions or dialysis, and who then developed hepatitis of unknown cause - meaning it was not caused by known hepatitis types A through E - 47 percent had antibodies to Vesivirus.
In separate tests that looked for actual virus in the blood, rather than antibodies, 5 percent of blood samples from normal donors showed Vesivirus. Among persons with evidence of liver damage, researchers found 11 percent had Vesivirus-contaminated blood.
"This study clearly demonstrates that both Vesivirus and the antibodies against it are fairly common in humans," said Alvin Smith, a professor of veterinary medicine at OSU and one of the world's leading experts on caliciviruses. "Vesivirus is widely distributed in many animal species, but this is a previously unrecognized relationship between Vesivirus and humans."
"This research also shows an increasing prevalence of Vesivirus antibody in persons who have hepatitis of unknown cause," Smith said. "This suggests there is a broader potential for Vesivirus infection and illness in humans than previously recognized."
Previous individual case reports have documented human disease with Vesivirus, said Dr. David O. Matson, a co-author on the study and physician at Eastern Virginia Medical School. "This study adds to our knowledge of the potential for Vesivirus illness in humans, a potential as-yet unstudied by others," Matson said.
There are assays available to test for Vesivirus infection or antibodies, researchers say, that have been developed at OSU and licensed to private industry.
"AVI BioPharma has investigated their proprietary NeuGene antisense as an anti-Vesiviral treatment, and is currently conducting further research and development," said Patrick Iversen, a co-author on the study and senior vice president of research and development at the company.
Researchers say that Vesivirus has natural reservoirs in the marine community where it can replicate and recycle, infecting and sometimes causing health problems in seals, sea lions, whales, and perhaps fish, shellfish and other species. In general, the marine environment is "a relatively under-explored potential reservoir of human pathogens," the researchers said in their study.
History suggests these viruses have rarely been confined to the ocean. A costly Vesivirus epidemic in hogs first was identified in 1932, and was found to be linked to uncooked fish and pork scraps fed to hogs. It's now known that that the same types of Vesiviruses - named in part for the disease they can cause in hogs, vesicular exanthema of swine - are found in many other species.
In a research article published in January in the American Journal of Veterinary Research, the same scientists found that 15 percent of the dairy and beef cattle in eight western states had antibodies to Vesivirus, with antibody prevalence in various herds ranging from zero to 80 percent. It concluded that Vesivirus infection in cattle is widespread, and in various studies has been "associated" - identified to be statistically relevant but not yet proven as a cause - with abortion, diarrhea, severe respiratory disease and vesicular disease.
In another study to be published soon, a population of Thoroughbred mares on horse farms in Kentucky, which was having an unusually high level of spontaneous abortions, was also found to have 81 percent positive testing for Vesivirus antibodies - far higher than a normal population.
Because of its endemic nature and prevalence, possible sources of Vesivirus infection in humans could include meat, seafood, contaminated water, contact exposure and blood transfusions, researchers say. Evidence suggests that Vesiviruses and other disease-causing caliciviruses are world wide, they said.
By David Stauth, 541-737-0787
Sources: Alvin Smith, 541-737-6532
Dr. David O. Matson, 757-668-6433
This research was supported by the Oregon Agricultural Experiment Station; the OSU Foundation, Laboratory for Calicivirus Studies Fund; AVI BioPharma; and the Center for Pediatric Research at Eastern Virginia Medical School.