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Researchers at The Ohio State University have discovered a potential new mode of transmission for the hepatitis E virus (HEV), suggesting it could be sexually transmitted. The study, published in PLOS Pathogens, found that HEV is associated with sperm in pigs, raising concerns about male infertility.

Hepatitis E is the leading cause of acute viral liver infection globally, particularly in developing regions with poor sanitation. While HEV is endemic in pigs in the United States, it primarily resides in organs rather than muscle and is killed during cooking.

Given HEV’s association with fatal pregnancy complications and reports of male infertility in the developing world, the research team, led by senior author Scott Kenney, investigated the virus’s infectivity in pigs, whose reproductive anatomy is similar to humans. The team inoculated pigs with HEV and discovered that the virus circulated in blood and was shed in feces, with the pigs remaining asymptomatic—mirroring many human cases.

Significantly, the study revealed that HEV was present on the head of sperm cells, and these viral particles could infect and replicate in human liver cells in culture. “Our study is the first one demonstrating this association of hepatitis E virus with the sperm cell,” said first author Kush Yadav.

Future studies aim to understand the mechanism of HEV’s association with sperm cells and whether sexual transmission occurs. Sexually transmitted organisms can find refuge in the testicles, protected by a blood-testis barrier that immune cells cannot cross. Besides reproductive disorders, HEV has been linked to pancreatic and neurological issues in humans. Clinical infections, including in pregnant individuals, have traditionally been traced to fecal-oral transmission.

Using fluorescence microscopy, Yadav detected viral particles in at least 19% of sperm cells from infected pigs 84 days after inoculation. However, whether these particles reside inside or outside the sperm cells remains unclear. Yadav noted, “We don’t know if the hepatitis E virus can actually complete a replication cycle in the sperm head, so we’re thinking sperm is more of a carrier than a susceptible cell.”

The study also found that HEV’s presence correlated with damaged sperm, potentially affecting their structure and motility. Although the researchers cannot definitively link these changes to fertility issues, the association between HEV infection and human infertility suggests a potential connection. “In between 20% and 50% of documented male infertility cases, they don’t really know what’s causing it,” Kenney said. “So we’re pushing for more screening for hepatitis E virus as a potential cause for those cases.”

These findings also underscore the need to screen sexual partners of pregnant women who test positive for HEV. Although sexual transmission hasn’t been confirmed, this precaution could prevent potential complications.

The implications for the swine industry are notable as well. Most commercial pig litters are produced through artificial insemination using donor sperm from large breeder facilities. Kenney highlighted that the endemic nature of HEV across the country might be linked to this practice. “That could be part of the problem with HEV being endemic across the country, and raises a question about whether it causes a reduction in the reproductivity of the pigs,” he said.

While the swine industry may not broadly vaccinate for HEV due to the lack of significant production losses, cost-effective screening or vaccination at breeder facilities could reduce the virus’s spread to new herds.

For more information, refer to the original study: Kush K. Yadav et al., Infectious hepatitis E virus is associated with the mature sperm head, PLOS Pathogens (2024).

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