Uterine Injury Caused by Genotype 4 Hepatitis E Virus Infection Based on a BALB/c Mice Model

Yang, Weimin; Chen, Shuangfeng; Mickael, Houfack Kenfack; Xu, Liangheng; Xia, Yueping; Cong, Chao; Zhang, Yike; Qian, Zhongyao; Li, Tengyuan; Wei, Du; Wu, Yu; Huang, Fen

doi:10.3390/v13101950

Cited by 11 publications

(14 citation statements)

References 61 publications

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“…In view of the adverse pregnancy and relatively high mortality of pregnant women caused by HEV, human trophoblast cells (JEG-3) were selected as an in vitro model. In addition, it has been reported that HEV can infect pregnant mice, causing miscarriage and uterine injury in female mice [ 29 ]. Therefore, whether HEV-3 could infect JEG-3 cells and the placenta of pregnant mice was first investigated.…”

Section: Resultsmentioning

confidence: 99%

Vital role of autophagy flux inhibition of placental trophoblast cells in pregnancy disorders induced by HEV infection

Yang,

Liu,

Tian

et al. 2023

Emerging Microbes & Infections

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Hepatitis E virus (HEV) has become one of the important pathogens that threaten the global public health. Type 3 and 4 HEV are zoonotic, which can spread vertically and cause placental damage. At the same time, autophagy plays an important role in the process of embryo development and pregnancy maintenance. However, the relationship between HEV and autophagy, especially in the placenta tissue, has not been clarified. We found lower litter rates in HEV-infected female mice, with significant intrauterine abortion of the embryo (24.19%). To explore the effects of HEV infection on placenta autophagy, chorionic cells (JEG-3) and mice placenta have been employed as research objects, while the expression of autophagy-related proteins (ATGs) has been detected in JEG-3 cells with different times of HEV inoculation. The results demonstrated that the expression of protein LC3 decreased and p62 accumulated, meanwhile ATGs such as ATG4B, ATG5, and ATG9A in JEG-3 cells have decreased significantly. In addition, the maturation of autophagosomes, which referred to the process of the combination of autophagosomes and lysosomes was prevented by HEV infection as well. All processes of autophagic flux, which include the initiation, development, and maturation three stages, were suppressed in JEG-3 cells after HEV infection. Similarly, the protein and gene expression of LC3 were significantly decreased in the placenta of pregnant mice with HEV infection. In summary, our results suggested that HEV inhibited autophagy in JEG-3 cells and placenta of pregnant mice, which might be the important pathogenic mechanisms of HEV infection leading to embryo abortion.

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Section: Resultsmentioning

confidence: 99%

Vital role of autophagy flux inhibition of placental trophoblast cells in pregnancy disorders induced by HEV infection

Yang,

Liu,

Tian

et al. 2023

Emerging Microbes & Infections

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“…They suggested that uterine damage in relation to endometrial thinning enhanced inflammatory response, and increased programmed cell death could be causative factors of pregnancy pathology. Moreover, they demonstrated the recovery of uterine layers and improvement in fertility after the clearance of HEV from female BALB/c mice [ 116 ].…”

Section: Characteristics Of An Ideal Model Recapitulating Hev Infecti...mentioning

confidence: 99%

Animal Models for Studying Congenital Transmission of Hepatitis E Virus

Yadav

Kenney

2023

Microorganisms

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One of the most intriguing issues in the hepatitis E virus (HEV) field is the significant increase in mortality rates of the mother and fetus when infection occurs in the second and third trimesters of gestation. A virus that is normally self-limiting and has a mortality rate of less than one percent in otherwise healthy individuals steeply rises by up to 30% in these pregnant populations. Answering this pivotal question has not been a simple task. HEV, in general, has been a difficult pathogen to understand in the laboratory setting. A historical lack of ability to efficiently propagate the virus in tissue culture models has led to many molecular aspects of the viral lifecycle being understudied. Although great strides have been made in recent years to adapt viruses to cell culture, this field remains behind other viruses that are much easier to replicate efficiently in vitro. Some of the greatest discoveries regarding HEV have come from using animal models for which naturally occurring strains of HEV have been identified, including pigs and chickens, but key limitations have made animal models imperfect for studying all aspects of human HEV infections. In addition to the difficulties working with HEV, pregnancy is a very complicated biological process with an elaborate interplay between many different host systems, including hormones, cardiovascular, kidneys, respiratory, gastrointestinal, epithelial, liver, metabolic, immune, and others. Significant differences between the timing and interplay of these systems are notable between species, and making direct comparisons between animals and humans can be difficult at times. No simple answer exists as to how HEV enhances mortality in pregnant populations. One of the best approaches to studying HEV in pregnancy is likely a combinatorial approach that uses the best combination of emerging in vitro and in vivo systems while accounting for the deficiencies that are present in each model. This review describes many of the current HEV animal model systems and the strengths and weaknesses of each as they apply to HEV pregnancy-associated mortality. We consider factors that are critical to analyzing HEV infection within the host and how, despite no perfect animal model for human pregnancy mortality existing, recent developments in HEV models, both in vitro and in vivo, are advancing our overall understanding of HEV in the pregnant host.

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“…However, it leads to chronic infection in immunocompromised patients, such as organ‐transplanted recipients 2 or patients with human immunodeficiency virus (HIV) infection 3 . Although HEV predominantly replicates in the liver, multiple extrahepatic HEV replication sites, including the brain, 4,5 placenta, 6,7 uterus, 8,9 testes, and epididymis, 10,11 have been identified. HEV RNA first detected in the sperm is associated with infertility 10,11 .…”

Section: Introductionmentioning

confidence: 99%

“…HEV replication in the placenta results in severe fibrosis and calcification, which is responsible for adverse pregnancy outcomes 7 . In addition, the replication of HEV in the uterus causes thinning endometrial thickness (EMT), severe inflammatory responses, and aggravated apoptosis also contribute to poor pregnancy 8 . However, the damage to the female genital tract caused by HEV infection is unclear.…”

Section: Introductionmentioning

confidence: 99%

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Infectious hepatitis E virus excreted into the vagina

Cong,

Xia,

Gong

et al. 2024

The FASEB Journal

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Hepatitis E virus (HEV) persists in the male genital tract that associates with infertility. However, the presence of HEV in the female genital tract is unreported. Vaginal secretions, cervical smears, and cervix uteri were collected to explore the presence of HEV in the female genital tract. HEV RNA and/or antigens were detected in the vaginal secretions, cervical smears, and the cervix uteri of women. The infectivity of HEV excreted into vaginal secretions was further validated in vitro. In addition, HEV replicates in the female genital tract were identified in HEV‐infected animal models by vaginal injection or vaginal mucosal infection to imitate sexual transmission. Serious genital tract damage and inflammatory responses with significantly elevated mucosal innate immunity were observed in women or animals with HEV vaginal infection. Results demonstrated HEV replicates in the female genital tract and causes serious histopathological damage and inflammatory responses.

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Uterine Injury Caused by Genotype 4 Hepatitis E Virus Infection Based on a BALB/c Mice Model

Cited by 11 publications

References 61 publications

Vital role of autophagy flux inhibition of placental trophoblast cells in pregnancy disorders induced by HEV infection

Vital role of autophagy flux inhibition of placental trophoblast cells in pregnancy disorders induced by HEV infection

Animal Models for Studying Congenital Transmission of Hepatitis E Virus

Infectious hepatitis E virus excreted into the vagina

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