High prevalence of hepatitis E virus in semen of infertile male and causes testis damage

Huang, Fen; Long, Feiyan; Wu, Yu; Situ, Jianwen; Fu, Lei; He, Zhanlong; Dong, Hao; Yang, Chenchen; Li, Yunlong; Yang, Fan; Wei, Du

doi:10.1136/gutjnl-2017-314884

Cited by 35 publications

(57 citation statements)

References 9 publications

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“…The pathogenesis and impact of HEV infection in the female genital system, especially in the absence of pregnancy, are unknown. Recent studies showed that HEV infection could cause testicular damage, germ cell apoptosis, and male infertility [22,23]. We showed here that HEV-1 induced the inflammatory response in PHESCs.…”

Section: Discussionsupporting

confidence: 56%

“…HEV-4 could disrupt the blood-testis barrier in the Mongolian gerbils' model and BALB/c mice, inducing the necrosis of tubules, germ cell apoptosis, and testicular damage [22,32]. In addition, HEV RNA was detected in pig semen in Shaanxi Province, China, and the semen of infertile males [23,33]. While others reported that there is no link between male infertility of HEV-3 infection [34].…”

Section: Discussionmentioning

confidence: 99%

“…The genital system is another target for HEV replication. The HEV-4 virus could cross the blood-testis barrier, causing severe testicular damage and infertility [22,23]. Similarly, HEV replicates efficiently in the ovary of the rabbits, inducing structural and molecular changes in the ovarian tissues and promoting oocyte apoptosis [24].…”

Section: Introductionmentioning

confidence: 99%

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Evidence of the Extrahepatic Replication of Hepatitis E Virus in Human Endometrial Stromal Cells

et al. 2020

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Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis worldwide. The tropism of HEV is not restricted to the liver, and the virus replicates in other organs. Not all the extrahepatic targets for HEV are identified. Herein, we found that non-decidualized primary human endometrial stromal cells (PHESCs), which are precursors for the decidua and placenta, are susceptible to HEV infection. PHESCs, isolated from healthy non-pregnant women (n = 5), were challenged with stool-derived HEV-1 and HEV-3. HEV RNA was measured by qPCR, and HEV capsid protein was assessed by flow cytometry, immunofluorescence (IF), and ELISA. HEV infection was successfully established in PHESCs. Intracellular and extracellular HEV RNA loads were increased over time, indicating efficient replication in vitro. In addition, HEV capsid protein was detected intracellularly in the HEV-infected PHESCs and accumulated extracellularly over time, confirming the viral assembly and release from the infected cells. HEV-1 replicated more efficiently in PHESCs than HEV-3 and induced more inflammatory responses. Ribavirin (RBV) treatment abolished the replication of HEV in PHESCs. In conclusion, PHESCs are permissive to HEV infection and these cells could be an endogenous source of HEV infection during pregnancy and mediate HEV vertical transmission.

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Section: Discussionsupporting

confidence: 56%

Section: Discussionmentioning

confidence: 99%

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Evidence of the Extrahepatic Replication of Hepatitis E Virus in Human Endometrial Stromal Cells

et al. 2020

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“…Of considerable interest is the discovery of the target gene, ubiquitously transcribed tetratricopeptide repeat‐containing, Y‐linked (UTY), which is associated with spermatogenesis. Huang et al recently reported high titers of HEV in the semen of infertile male. Moreover, they identified the testis and epididymis as probable sites of HEV replication and theorized the resulting destruction of the seminiferous epithelium and Leydig cells to cause multiple sperm abnormalities .…”

Section: Discussionmentioning

confidence: 99%

“…Huang et al recently reported high titers of HEV in the semen of infertile male. Moreover, they identified the testis and epididymis as probable sites of HEV replication and theorized the resulting destruction of the seminiferous epithelium and Leydig cells to cause multiple sperm abnormalities . In our study, the miRNA‐dependent gene silencing of UTY indicates a possible role in these processes.…”

Section: Discussionmentioning

confidence: 99%

Computational identification of hepatitis E virus‐encoded microRNAs and their targets in human

Baruah

Bose

2019

Journal of Medical Virology

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microRNAs (miRNAs) are small, noncoding RNAs which regulate eukaryotic gene expression via RNA interference pathway. Recently, miRNAs have been identified in a number of viruses with current evidence suggesting that they regulate gene expression in both virus and host. This makes viral miRNAs potential targets of clinical intervention, with the possibility of inhibiting aberrant host gene expression associated with the disease. In this study, computational approaches were taken to scan the hepatitis E virus (HEV) genome for putative pre-miRNA molecules, which were then analyzed for the presence of mature miRNAs. The 3′untranslated region (3′-UTR) and 5′-UTR sequences targeted by these miRNAs were identified using Miranda computational tool, followed by the functional annotation of the associated messenger RNAs (mRNAs) using Gene Ontology terms and Kyoto Encyclopaedia of Genes and Genomes pathway analysis. We identified a total of nine viral encoded miRNAs in HEV. After functional annotation, the majority of the viral miRNA targets were found to be associated with cell cycle, cell differentiation, nitrogen compound metabolism, transmembrane transport, and chromosome organization. This in-silico study identified putative viral miRNAs encoded by HEV and their potential human mRNAs targets.These viral miRNAs have the potential to affect host gene expression as well as viral life cycle and pathogenesis and can, therefore, serve as potential therapeutic targets during HEV infection. K E Y W O R D S hepatitis E, microRNA, messenger RNA, RNA interference 1 | BACKGROUND microRNAs (miRNAs) are small, noncoding RNAs that regulate gene expression in eukaryotes. The 60 to 80-nucleotide (nt) precursor miRNA (pre-miRNA) is of intronic origin and is cleaved in the cytoplasm by the RNAse III enzyme Dicer to yield the 21 to 23-nt long miRNA. These miRNAs interact with the multiprotein RNA-induced silencing complex and can bind specific cellular mRNAs based on sequence complementarity. Depending on the extent of complementarity, the translation of the messenger RNA (mRNA) may be reduced or completely silenced, with the mRNA being marked for destruction. 1 While the regulatory function of miRNAs is well documented in eukaryotes, there have not been many reports on virally encoded miRNAs, with preliminary reports identifying miRNAs in herpes simplex virus type 1, human adenovirus, dengue virus, West Nile virus, porcine reproductive and respiratory syndrome virus, and human cytomegalovirus. 2-8 J Med Virol. 2019;91:1545-1552. wileyonlinelibrary.com/journal/jmv

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Model systems for studying extrahepatic pathogenesis of hepatitis E virus. Current knowledge and future directions

El‐Mokhtar

Sayed

2021

Reviews in Medical Virology

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Summary Hepatitis E Virus is the most common cause of acute viral hepatitis globally. HEV infection is endemic in developing countries. Also, autochthonous and sporadic cases are reported in developed countries. HEV causes acute and chronic infections. Besides, extrahepatic manifestations including neurological, renal, haematological, acute pancreatitis and complications during pregnancy are associated with HEV infections. The pathogenesis of HEV in the extrahepatic tissues is either due to direct cytopathic effect mediated by the virus replication, or immunological mechanisms caused by an uncontrollable host response. Researchers have used different in vivo and in vitro models to study the pathogenesis of HEV in the extrahepatic tissues and analyse the host immune response against HEV infection. This review highlights the extrahepatic disorders associated with HEV infection. We focused on the in vivo and in vitro models as a tool for elucidating the HEV infection beyond the liver and studying the mechanisms of HEV induced tissue damages.

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High prevalence of hepatitis E virus in semen of infertile male and causes testis damage

Cited by 35 publications

References 9 publications

Evidence of the Extrahepatic Replication of Hepatitis E Virus in Human Endometrial Stromal Cells

Evidence of the Extrahepatic Replication of Hepatitis E Virus in Human Endometrial Stromal Cells

Computational identification of hepatitis E virus‐encoded microRNAs and their targets in human

Model systems for studying extrahepatic pathogenesis of hepatitis E virus. Current knowledge and future directions

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