Hepatitis E virus infects human testicular tissue and Sertoli cells

Liu, Tianxu; Cao, Yalei; Weng, Jiaming; Gao, Songzhan; Jin, Zirun; Zhang, Yun; Yang, Yuzhuo; Zhang, He; Xia, Changyou; Yin, Xin; Luo, Yong; He, Qiyu; Jiang, Hui; Wang, Lin; Zhang, Zhe

doi:10.1080/22221751.2024.2332657

Cited by 2 publications

(1 citation statement)

References 39 publications

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“…Despite multiple studies attempting to delineate the mechanism behind pregnancy mortality, a definitive answer is yet to be found. Recent discoveries demonstrating ability of HEV to replicate in the vagina [13] and human male testicular cells [14] demonstrates a new infection scenario that needs detailed investigation and its association with pregnancy mortality. Our study demonstrating infectious HEV in the sperm head raises concerns on a potentially new route of HEV transmission in humans.…”

Section: Plos Pathogensmentioning

confidence: 99%

Infectious hepatitis E virus is associated with the mature sperm head

Yadav,

Boley,

Laocharoensuk

et al. 2024

PLoS Pathog

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Hepatitis E virus (HEV) is the leading cause of acute viral hepatitis worldwide. HEV associated pregnancy mortality has been reported as up to 30% in humans. Recent findings suggest HEV may elicit effects directly in the reproductive system with HEV protein found in the testis, viral RNA in semen, and viral replication occurring in placental cell types. Using a natural host model for HEV infection, pigs, we demonstrate infectious HEV within the mature spermatozoa and altered sperm viability from HEV infected pigs. HEV isolated from sperm remained infectious suggesting a potential transmission route via sexual partners. Our findings suggest that HEV should be explored as a possible sexually transmittable disease. Our findings propose that infection routes outside of oral and intravenous infection need to be considered for their potential to contribute to higher mortality in HEV infections when pregnancy is involved and in HEV disease in general.

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Section: Plos Pathogensmentioning

confidence: 99%

Infectious hepatitis E virus is associated with the mature sperm head

Yadav,

Boley,

Laocharoensuk

et al. 2024

PLoS Pathog

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A porcine chronic hepatitis E virus (HEV) infection model exhibits HEV replication in male accessory reproductive glands and immune-mediated reproductive damage

Yadav,

Boley,

Laocharoensuk

et al. 2024

Preprint

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Hepatitis E virus (HEV) is an expanding zoonotic viral disease threat. Although HEV causes acute viral hepatitis, it is increasingly being recognized as a systemic pathogen with detection and damage in extrahepatic tissues. The presence of HEV RNA in the semen of chronically infected human patients in the absence of viremia and fecal shedding and presence of HEV in the sperm head underscores the need to understand the interaction of HEV within the male reproduction system. Male accessory glands secrete biofluids necessary for sperm nourishment and to neutralize the acidity of the vagina. The role of male accessory glands in the dissemination and persistence of HEV infection have not been studied. Using an immunosuppressed pig model for chronic HEV infection, we demonstrate infectious HEV in mature sperm cells altering the sperm motility and morphology. HEV isolated from sperm cells remained infectious in human hepatoma cells. Spermatic fluid contained lower virus titers than the sperm cells from chronically infected pigs highlighting that the sperm cells themselves can associate with the virus. Evaluation of the male accessory glands demonstrated viral replication, infiltration of CD45 leukocytes, and apoptosis associated with HEV infection. A decrease in serum testosterone levels was evident in the HEV infected pigs. Even though a lower viral RNA titer was seen in serum and feces of chronically infected, immunosuppressed and ribavirin treated pigs, high viral RNA and infectious particles in sperm is a concern. Our findings necessitate further studies defining the mechanism of sperm cell invasion by HEV, length of HEV survival in sperm cells during chronic HEV infection, and risk of sexual transmission of HEV during both acute and chronic phases of infection.Author SummaryHepatitis E virus, a leading cause of acute viral hepatitis, causes both acute and chronic infection in humans. Recent advances within the HEV field have demonstrated extrahepatic diseases associated with HEV. More recent findings have revealed infectious HEV in the vagina, Sertoli cells, and ejaculate of humans, and sperm cells of pigs. We demonstrate that the male accessory sex glands may have a role in the persistence of HEV infection during chronic infections. We utilized an established immunosuppressed pig model and treated pigs with ribavirin to study the presence of virus in the sperm cells. We demonstrated high viral RNA loads and infectious particles associated with sperm cells. Our study further highlights the importance of the testis, as an immune privileged site, in the maintenance of chronic HEV infection. New studies to evaluate the mechanisms by which HEV associates with sperm cells, the length of HEV survival in sperm cell fractions, and consideration of the testes as a potential HEV reservoir are necessary.

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Hepatitis E virus infects human testicular tissue and Sertoli cells

Cited by 2 publications

References 39 publications

Infectious hepatitis E virus is associated with the mature sperm head

Infectious hepatitis E virus is associated with the mature sperm head

A porcine chronic hepatitis E virus (HEV) infection model exhibits HEV replication in male accessory reproductive glands and immune-mediated reproductive damage

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