Hepatitis E virus: reasons for emergence in humans

Sooryanarain, Harini; Meng, Xiang‐Jin

doi:10.1016/j.coviro.2018.11.006

Cited by 51 publications

(44 citation statements)

References 105 publications

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“…Hepatitis E infections are caused by a small (27-34 nm), positive-sense, single-stranded RNA virus (approx. 7.2 kb size) that belongs to the Hepeviridae family (Sooryanarain and Meng, 2019;Van der Poel and Rzezutka, 2019). HEV is excreted in feces as non-enveloped virions but circulates in the blood in a membrane-associated, quasi-enveloped form (Yin et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

HEV Occurrence in Waste and Drinking Water Treatment Plants

et al. 2020

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Hepatitis E virus (HEV), particularly zoonotic genotype 3, is present in environmental waters worldwide, especially in industrialized countries. Thus, monitoring the presence of HEV in wastewater treatment plants (WWTPs) is an emerging topic due to the importance of reusing water on a global level. Given the limited data, this study aimed to monitor the occurrence of HEV in influent and effluent water in waste-and drinkingwater treatment plants (WWTPs and DWTPs). To this end, different procedures to concentrate HEV in influent and effluent water from WWTPs and DWTPs were initially evaluated. The evaluated procedures resulted in average HEV recoveries of 15.2, 19.9, and 16.9% in influent, effluent, and drinking water samples, respectively, with detection limits ranging from 10 3 to 10 4 international units (IU)/L. Then, a one-year pilot study was performed to evaluate the performance of the selected concentration method coupled with three RT-qPCR assays in influent and effluent water samples from four different WWTPs. HEV prevalence in influent water varied based on both the RT-qPCR assay and WWTP, while HEV was not detected in effluent water samples. In addition, HEV prevalence using only RT-qPCR3 was evaluated in influent (n = 62) and effluent samples (n = 52) from four WWTPs as well as influent (n = 28) and effluent (n = 28) waters from two DWTPs. The present study demonstrated that HEV circulated in the Valencian region at around 30.65% with average concentrations of 6.3 × 10 3 IU/L. HEV was only detected in influent wastewater samples, effluent samples from WWTPs and influent and effluent samples from DWTPs were negative. However, given that the infective dose in waterborne epidemics settings is not yet known and the low sensibility of the assay, unfortunately, no direct conclusion could be achieved on the risk assessment of environmental contamination.

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Section: Introductionmentioning

confidence: 99%

HEV Occurrence in Waste and Drinking Water Treatment Plants

et al. 2020

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“…HEV−1 and HEV−2 are restricted to humans and are prevalent in regions with poor water sanitation, such as the developing countries of Asia, Africa, South and Central America (Hartl et al, 2016;Pisano et al, 2018). On the other hand, HEV-3 and HEV-4 are considered to be zoonotic pathogens as they have a much wider range of mammalian hosts including, among others, domestic and wild swine and ruminants (Park et al, 2016;Sooryanarain and Meng, 2019). Hepatocytes have been identified as the primary sites of HEV replication, but the virus has been detected in other tissues such as epithelial cells of the small intestine, placenta, and muscle (Williams et al, 2001;Bose et al, 2014;Salines et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of High-Pressure Processing in Inactivation of the Hepatitis E Virus

et al. 2020

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Hepatitis E virus (HEV) causes acute hepatitis with approximately 20 million cases per year globally. Based on genetic diversity, HEV is classified into different genotypes, with genotype 3 (HEV-3) being most prevalent in Europe and North America. The transmission of HEV-3 has been shown to be zoonotic and mainly associated with the consumption of raw or undercooked pork products. Herein, we investigated the efficacy of high-pressure processing (HPP) in inactivation of HEV-3 using a cell culture system. HPP has been indicated as a promising non-thermal pathogen inactivation strategy for treatment of certain high-risk food commodities, without any noticeable changes in their nature. For this purpose, we treated HEV-3 in media with different conditions of HPP: 400 MPa for 1 and 5 min, as well as 600 MPa for 1 and 5 min, at ambient temperature. All four HPP treatments of HEV in media were observed to result in a 2-log reduction in HEV load, as determined by the amounts of extracellular HEV RNA produced at 14-day post-infection, using the A549/D3 cell culture system. However, application of the same treatments to artificially contaminated pork pâté resulted in 0.5 log reduction in viral load. These results indicate that the efficacy of HPP treatment in the inactivation of HEV-3 is matrix-dependent, and independent of maximum pressure between 400 and 600 MPa and hold time between 1 and 5 min. Based on the obtained results, although the HPP treatment of pork pâté reduces the HEV-3 load, it might not be sufficient to fully mitigate the risk.

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“…The species Orthohepevirus A includes virus strains that infect humans and is subclassified into at least eight different genotypes (1). Genotypes 1 to 4 HEVs are of significant human health importance (2). Genotypes 1 and 2 HEVs infect only humans, usually establish acute infection associated with large explosive outbreaks, and can cause an increased mortality in infected pregnant women (3).…”

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The U-Rich Untranslated Region of the Hepatitis E Virus Induces Differential Type I and Type III Interferon Responses in a Host Cell-Dependent Manner

Sooryanarain

Heffron

Meng

2020

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Hepatitis E virus (HEV), a single-strand positive-sense RNA virus, is an understudied but important human pathogen. The virus can establish infection at a number of host tissues, including the small intestine and liver, causing acute and chronic hepatitis E as well as certain neurological disorders. The retinoic acid-inducible gene I (RIG-I) pathway is essential to induce the interferon (IFN) response during HEV infection. However, the pathogen-associated motif patterns (PAMPs) in the HEV genome that are recognized by RIG-I remain unknown. In this study, we first identified that HEV RNA PAMPs derived from the 3′ untranslated region (UTR) of the HEV genome induced higher levels of IFN mRNA, interferon regulatory factor-3 (IRF3) phosphorylation, and nuclear translocation than the 5′ UTR of HEV. We revealed that the U-rich region in the 3′ UTR of the HEV genome acts as a potent RIG-I PAMP, while the presence of poly(A) tail in the 3′ UTR further increases the potency. We further demonstrated that HEV UTR PAMPs induce differential type I and type III IFN responses in a cell type-dependent fashion. Predominant type III IFN response was observed in the liver tissues of pigs experimentally infected with HEV as well as in HEV RNA PAMP-induced human hepatocytes in vitro. In contrast, HEV RNA PAMPs induced a predominant type I IFN response in swine enterocytes. Taken together, the results from this study indicated that the IFN response during HEV infection depends both on viral RNA motifs and host target cell types. The results have important implications in understanding the mechanism of HEV pathogenesis. IMPORTANCE Hepatitis E virus (HEV) is an important human pathogen causing both acute and chronic viral hepatitis E infection. Currently, the mechanisms of HEV replication and pathogenesis remain poorly understood. The innate immune response acts as the first line of defense during viral infection. The retinoic acid-inducible gene I (RIG-I)-mediated interferon (IFN) response has been implicated in establishing antiviral response during HEV infection, although the HEV RNA motifs that are recognized by RIG-I are unknown. This study identified that the U-rich region in the 3′ untranslated region (UTR) of the HEV genome acts as a potent RIG-I agonist compared to the HEV 5′ UTR. We further revealed that the HEV RNA pathogen-associated motif patterns (PAMPs) induced a differential IFN response in a cell type-dependent manner: a predominantly type III IFN response in hepatocytes, and a predominantly type I IFN response in enterocytes. These data demonstrate the complexity by which both host and viral factors influence the IFN response during HEV infection.

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Hepatitis E virus: reasons for emergence in humans

Cited by 51 publications

References 105 publications

HEV Occurrence in Waste and Drinking Water Treatment Plants

HEV Occurrence in Waste and Drinking Water Treatment Plants

Evaluation of High-Pressure Processing in Inactivation of the Hepatitis E Virus

The U-Rich Untranslated Region of the Hepatitis E Virus Induces Differential Type I and Type III Interferon Responses in a Host Cell-Dependent Manner

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