The hepatitis E virus can be sexually transmitted and can also be associated with male infertility

The discovery that the hepatitis E virus is linked to pig semen suggests that the virus is both sexually transmitted and linked to male infertility, according to a new study.

Hepatitis E (HEV) is the most common cause of acute viral liver infections in humans worldwide, especially in developing countries with poor sanitation conditions. The virus is also widespread in pigs in the USA – but it is mainly found in organs rather than muscles and is killed when the meat is cooked.

Because HEV has been linked to fatal pregnancy complications and reports of male infertility in developing countries, researchers at Ohio State University investigated the virus’s infectivity in pigs, whose reproductive anatomy closely resembles that of humans.

After the team vaccinated pigs with HEV, they found that the virus was circulating in the blood and being excreted in the feces. This means that the pigs were infected but showed no clinical symptoms – asymptomatic cases are also common in humans. The results also showed that HEV was present on the head of sperm and that the same virus particles could infect human liver cells in culture and begin to replicate.

“Our study is the first to demonstrate this link between the hepatitis E virus and the sperm cell,” said lead author Kush Yadav, who completed the work as a doctoral student at the Center for Food Animal Health at Ohio State University. “Our future studies will be aimed at understanding the link between the hepatitis E virus and the sperm head more mechanistically and using animal models to see if sexual transmission of the virus occurs – because in the human setting we don’t yet know that.”

The study was recently published in the journal PLOS pathogens.

Sexually transmitted organisms are those that find a safe haven in the testes, where they are protected by a blood-testis barrier that immune cells cannot cross. In addition to pregnancy and reproductive disorders associated with HEV, there is evidence that it can also cause pancreatic and neurological disorders in humans. In the past, clinical infections – even in pregnant women – were thought to be due to fecal-oral transmission.

Yadav works in the lab of lead study author Scott Kenney, an associate professor of veterinary preventive medicine at Ohio State University in the Center for Food Animal Health in the College of Food, Agricultural, and Environmental Sciences on the Wooster campus.

Kenney studies HEV and other viruses in animals – particularly those that can infect humans. This work is an offshoot of a larger study in pigs that examined HEV strains that are resistant to antivirals.

In this new study, Yadav examined pig semen 84 days after vaccination with HEV using fluorescence microscopy and discovered virus particles associated with at least 19% of the sperm cells collected from the infected pigs.

“We can’t say whether they are outside or inside the sperm cells,” he said. “We don’t know if the hepatitis E virus can actually complete a replication cycle in the sperm head, so we assume that sperm are carriers rather than susceptible cells.”

The study also showed that the presence of HEV correlated with damaged sperm – potentially altering their structure and reducing their ability to move through semen. However, researchers cannot yet say whether these changes directly lead to fertility problems, although the link between HEV infection and human infertility suggests this.

In 20 to 50% of documented cases of male infertility, the cause is not really known. That is why we are pushing for more testing for the hepatitis E virus as a possible cause of these cases.”

Scott Kenney, lead study author

The current findings also form the basis for screening the sexual partners of pregnant women who test positive for HEV, Yadav said, even though scientists have not yet proven that sexual transmission is possible.

This also has consequences for the pig industry. Most commercial pig litters are produced through artificial insemination, with donor semen being widely distributed from large breeding facilities.

“That may be part of the problem that HEV is endemic across the country and raises the question of whether it is leading to a reduction in the reproductive capacity of pigs,” Kenney said. “Because HEV does not cause enough damage to pigs to limit the profitability of production, I don’t think the swine industry will be vaccinating against hepatitis E virus across the board. However, if we could do some sort of low-cost screening or vaccination in these upstream boar operations, we could potentially reduce the introduction of the virus into new herds.”

This work was supported by state and federal funds awarded to the Ohio Agricultural Research and Development Center and the National Institute of Allergy and Infectious Diseases.

Other co-authors include Patricia Boley, Thamonpan Laocharoensuk, Saroj Khatiwada, Carolyn Lee, Menuka Bhandari and Juliette Hanson of Ohio State and Lindsey Moore of the College of Wooster.