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Journal of General Virology header logo Journal of General Virology

Volume 107, Issue 4

Sexual transmission of hepatitis E virus via vaginal and rectal routes in a rabbit model Open Access

Abstract

Hepatitis E virus (HEV) is a major cause of acute hepatitis worldwide. While faecal–oral transmission is well-established, the potential for sexual transmission remains unclear. This study aimed to investigate whether HEV can be transmitted through sexual routes using a rabbit model. A total of 80 rabbits were inoculated intravaginally or intrarectally with HEV, compared to intravenous challenge. To assess hormonal influence, rabbits were pre-treated with medroxyprogesterone acetate (MPA) or pregnant mare serum gonadotrophin (PMSG) prior to vaginal inoculation. Also, 12 pregnant rabbits were injected with HEV by vaginal and intravenous routes, respectively, to evaluate adverse outcomes. Viral shedding, seroconversion, viral loads in tissues, histopathology and vaginal microbiota were analysed. Our results showed that HEV can be transmitted through both vaginal and rectal routes, establishing productive but less efficient infections than intravenous inoculation. Crucially, the MPA dramatically enhanced vaginal susceptibility, leading to prolonged viral shedding, higher systemic viral loads and 100% seroconversion, compared to partial infection in PMSG-treated and untreated controls. Vaginal infection in pregnant rabbits resulted in significant adverse outcomes, including abortion (66.7%) and vertical transmission. Furthermore, vaginal inoculation altered the local microbiota and transcriptome, suggesting a remodelled genital tract microenvironment. Our study provided the first direct experimental evidence that HEV can be sexually transmitted via vaginal and rectal routes. The progesterone-mediated enhancement of susceptibility and the severe pregnancy outcomes highlighted its public health risk, particularly for women.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): adverse pregnancy outcomes , animal models , hepatitis E virus , pregnancy and sexual transmission
Funding
This study was supported by the:
  • National Natural Science Foundation of China (Award 82202504)
    • Principal Award Recipient: ManyuLi
  • National Postdoctoral Program for Innovative Talents (Award 88032Y0008)
    • Principal Award Recipient: QiyuHe
  • China Postdoctoral Science Foundation (Award 88014Y0236)
    • Principal Award Recipient: QiyuHe
© 2026 The Authors
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License.
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2026-04-01
2026-04-22

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Sexual transmission of hepatitis E virus via vaginal and rectal routes in a rabbit model
J. Gen. Virol. 107, 002231 (2026); https://doi.org/10.1099/jgv.0.002231
/content/journal/jgv/10.1099/jgv.0.002231
/content/journal/jgv/10.1099/jgv.0.002231
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