Hepatitis E virus (HEV) is the leading cause of acute viral hepatitis globally. In the last few decades, HEV has been described as causing extrahepatic clinical manifestations including neurological, pancreatic, and reproductive disorders. Recent findings have demonstrated HEV in the testes and viral RNA in semen. In addition, HEV replication has been shown in human testicular explants, Sertoli cells, and in the vaginal tissue of rabbits. These findings coupled with infectious HEV in sperm requires understanding of HEV as a potential contributor in reproductive health and as a sexually transmittable disease (STD).
A recent study led by Dr. Kush Kumar Yadav under the direction of Associate Prof. Dr. Scott P. Kenney from The Ohio State University, United States identified the association of infectious HEV with the sperm head. They used a natural HEV host, the pig, infected with the genotype 3 zoonotic strain of Paslahepevirus balayani (US-2 isolate) as a model to investigate the presence of HEV in sperm cells. They further assessed the infectiousness of virus within sperm cells using a human liver cell culture system to understand the potential transmission ability of HEV via sperm cells.
Semen samples were harvested from the epididymis of experimentally infected pigs that had become sub-clinically infected by using an aspiration and flushing technique. The researchers aimed to understand the effect of HEV on the sperm quality. They observed a decrease in progressive motility and altered morphology in US-2 HEV (human HEV) infected pig sperm specimens. They next sought to delineate the relationship of the virus with the mature spermatozoa. Spermatic fluid and sperm cells were separated, and testing indicated a higher viral RNA presence in the sperm cells than spermatic fluid. In addition, they demonstrated the direct association of HEV antigen in the acrosomal region of the sperm head. The infectiousness of the sperm cell associated HEV was assessed using HepG2/C3A (human liver) cells. Lysates from infected spermatozoa contained infectious HEV capable of infecting human liver cells highlighting a need to screen human semen samples in geographical regions where endemic HEV causing pregnancy mortality has been reported. Based on the findings, the authors concluded that HEV infection routes outside of oral and intravenous infection need to be considered for their contribution in disease transmission and mortality.
These results suggest that the pig model can be used to study HEV-induced sperm health disorders that have been observed in humans. Future studies demonstrating the mechanisms underlying spermatozoa infection, duration of the virus presence and infectious virus shed in the sperm head, and how these factors contribute to HEV spread and pregnancy mortality need to be undertaken. Sexual transmission should also be considered from a swine husbandry standpoint where it could be a potential mechanism for introduction to new herds.
Dr. Kush Kumar Yadav will be joining Dr. XJ Meng’s lab as a Post Doctoral Associate, at the Department of Biomedical Science, College of Veterinary Medicine, Virginia Tech University. He gained 6 years of valuable experience working with HEV during his graduate career (MS and PhD) under the supervision of Dr. Kenney.
Dr. Scott P. Kenney is an Associate Professor, at Center for Food Animal Health, Department of Animal Sciences, Department of Veterinary Preventive Medicine, The Ohio State University.
Read the full article published in PLOS Pathogens (2024 May 20;20(5):e1012240): Infectious hepatitis E virus is associated with the mature sperm head | PLOS Pathogens
