New research suggests that pigs may be a vehicle for transmitting a strain of hepatitis E virus (HEV) common in rats that has recently been found to infect humans.
He Rocahepevirus ratti The strain is called “rat HEV” because rats are the main reservoir of the virus. Since the first human case was reported in a person with a suppressed immune system in Hong Kong in 2018, at least 20 human cases in total have been reported, including in people with normal immune function.
People infected with rat hepatitis E virus did not report exposure to rats, so the cause of infection has not been defined. The suspected cause of other human infections with hepatitis E virus in many cases is the consumption of raw pork, making this also a possible route of transmission of rat hepatitis E virus.
Researchers at Ohio State University found that a strain of rat hepatitis E virus isolated from humans could infect pigs and was transmitted among animals raised in farm-like conditions. Rats are common pests on pig farms, suggesting that the pork production industry may be an environment in which rat hepatitis E virus could reach humans.
“We always want to know what viruses might be on the rise, so we need to know the genetics behind this virus in the unlikely event that something happens in the United States that allows rat HEV to spread,” said senior author Scott Kenney, an associate professor of veterinary preventive medicine at Ohio State based in the Center for Food Animal Health on the Wooster campus of the College of Food, Agricultural and Environmental Sciences.
The study was recently published in PNAS Nexus.
Hepatitis E is the leading cause of acute viral liver infection in humans worldwide, especially in developing regions where sanitary conditions are poor. The virus is also endemic in pigs in the United States, although it is present primarily in the liver and not in the muscles, and is killed when the meat is cooked.
Previous studies testing cross-species infectivity of rat HEV showed that the strain used in the experiments did not infect non-human primates.
“It went undetected for six or seven years because it was thought not to be a human pathogen. And now it’s infecting humans, so we need to figure out why,” Kenney said.
One strain linked to human disease is known as LCK-3110. First author Kush Yadav, who completed this work as a PhD student at the Center for Food Animal Health, used the viral genome sequence to construct an infectious clone of LCK-3110.
The team first demonstrated that the cloned virus could replicate in multiple types of human and mammalian cell cultures and in pigs. The researchers then injected the pigs with an infectious solution containing either the LCK-3110 strain or another HEV strain present in pigs in the U.S., as well as saline as a control condition.
One week later, viral particles were detected in the blood and faeces of both groups receiving HEV strains, but levels were higher in pigs infected with rat HEV. Two weeks later, pigs housed in the same barn that did not receive inoculations also began shedding rat HEV in their faeces, indicating that the virus had spread via the faecal-oral route.
Although organs and body fluids from infected pigs also tested positive for viral RNA, the animals showed no signs of illness. Previous research suggests that rats also show no clinical symptoms.
Still, rat HEV was detected in the spinal fluid of infected pigs, a finding that coincides with growing concern that several strains of HEV that infect humans can damage the brain. One human death linked to rat HEV was caused by meningoencephalitis.
“HEV is gaining importance in the treatment of neurological disorders, and much of the current research points to the neuropathology being caused by the hepatitis E virus,” Yadav said. “And while we have a small number of known human cases, a high percentage of them are immunosuppressed. That means transplant recipients in the United States could be at risk for infection with general HEV as well as rat HEV.”
“Research could now focus on whether pig liver products contain rat HEV and explore food safety procedures to block the disease.”
Yadav is now a postdoctoral researcher at Virginia Tech’s Virginia-Maryland College of Veterinary Medicine. Co-authors of the study, all from Ohio State University, were Patricia Boley, Carolyn Lee, Saroj Khatiwada, Kwonil Jung, Thamonpan Laocharoensuk, Jake Hofstetter, Ronna Wood and Juliette Hanson.