Recent studies indicate that pigs might act as carriers for a version of the hepatitis E virus (HEV) prevalent in rats, which has recently been discovered to infect humans.
The strain known as Rocahepevirus ratti, or “rat HEV,” derives its name from rats being its main reservoir. The first case in humans was reported in a person with a compromised immune system in Hong Kong in 2018, and since then, there have been at least 20 additional cases, including individuals with normal immune systems.
Interestingly, those infected with rat HEV have not reported any contact with rats, leaving the source of infection unclear. Typically, in other HEV cases, a common transmission route is the consumption of raw pork, which might also apply to rat HEV.
Researchers from The Ohio State University discovered that a strain of rat HEV taken from humans could infect pigs and spread among pigs housed together under farming conditions. Rats are prevalent in pig farming environments, indicating that the pork production sector could be a pathway for the rat HEV to reach humans.
Scott Kenney, a senior author and associate professor of veterinary preventive medicine at Ohio State, emphasized that understanding the genetics of this virus is crucial for anticipating any potential public health issues in the United States that could result from rat HEV becoming more widespread.
This study was recently published in PNAS Nexus.
Hepatitis E is a leading cause of acute viral liver infections in people globally, especially in developing countries with inadequate sanitation. In the U.S., the virus is also found in pigs, mostly located in the liver and rendered inactive through proper cooking of meat.
Previous research evaluating the ability of rat HEV to infect other species indicated that the strain tested did not pose a threat to non-human primates.
Kenney noted that rat HEV seemed to have fallen off the radar for several years as it was not considered a human pathogen, but now that it is causing infections, it is important to investigate the reasons behind this shift.
A specific strain that has been associated with human illness is called LCK-3110. Kush Yadav, the primary author and a PhD student in the Center for Food Animal Health, utilized the viral genomic sequence to create an infectious clone of LCK-3110.
The research team demonstrated that the cloned virus was capable of replicating in various human and animal cell cultures, as well as in pigs. They then injected pigs with either an infectious solution containing the LCK-3110 strain, another HEV strain found in pigs in the U.S., or saline as a control.
After one week, viral particles were discovered in the blood and feces of both groups that received HEV strains, with higher levels in pigs infected with rat HEV. By two weeks, pigs housed together that did not receive any injections also began shedding rat HEV in their feces, indicating that the virus had spread through fecal-oral transmission.
Although the organs and bodily fluids of the infected pigs also tested positive for viral RNA, the animals showed no signs of illness. Similar findings suggest that rats do not display clinical symptoms either.
Nonetheless, the presence of the rat HEV virus was confirmed in the cerebrospinal fluid of the infected pigs, which raises concerns about the neurological effects of certain HEV strains on humans. One human fatality linked to rat HEV was associated with meningoencephalitis.
Yadav explained that HEV’s role in neurological disorders is becoming increasingly significant, with current research suggesting that hepatitis E virus could lead to neurological damage. Moreover, a significant proportion of known human cases involve immunosuppressed individuals, highlighting the potential risk for transplant recipients in the U.S. from both standard HEV and rat HEV.
Future research may focus on determining whether pork liver products carry rat HEV and investigate food safety measures to prevent its spread.
Yadav has continued his research as a postdoctoral researcher at the Virginia-Maryland College of Veterinary Medicine at Virginia Tech. The other co-authors of this study from Ohio State include Patricia Boley, Carolyn Lee, Saroj Khatiwada, Kwonil Jung, Thamonpan Laocharoensuk, Jake Hofstetter, Ronna Wood, and Juliette Hanson.
