Introduction: Hepatitis E virus (HEV) infection is caused by viruses belonging to the Hepeviridae family. HEV infection can be self-limiting; however, extrahepatic manifestations may be present. The purpose of the current study was to establish the seroprevalence of HEV among Bulgarian liver transplant recipients (LTRs) and to identify associated risk factors. Materials & Methods: The present study was conducted between April 1, 2023, and October 30, 2023, at the Military Medical Academy, Sofia, Bulgaria. All serum samples were tested for anti-HEV IgG/IgM using HEV IgG/IgM enzyme-linked immunosorbent assay on Dia.Pro (Milan, Italy). Each participating LTR completed a detailed paper-based closed-ended questionnaire regarding the associated risk factors for HEV infection. Results: The study included 73 LTRs with a mean age of 47.0 ± 14.0 years. Anti-HEV IgG antibodies were detected in 25 LTRs (34.2%), including 20 males (37.7%) and 5 females (25%). All participants were HEV-IgM negative. HEV seropositivity rates were higher but not statistically significant in LTRs aged >60 years than in those aged <60 years (40% vs. 32.7%). A significant factor by logistic regression was "high level of education" (odds ratio [OR] = 2.917; p = 0.038). Conclusion: To the best of our knowledge, this is the first seroepidemiological HEV study among LTRs from Bulgaria that found a high seroprevalence (34.2%).

China, especially the Chinese mainland, is a highly endemic area of hepatitis E, and its incidence rate has been increasing in recent years. Hepatitis E virus (HEV) is the causative agent of hepatitis E, with a variety of domestic animals as potential hosts. The shift in the main epidemic strain and the increasing trend of zoonotic HEV infection in the Chinese mainland need urgent attention. This systematic review aimed to provide a summary of HEV detection and its characteristics in domestic animals in the Chinese mainland.

A total of 1,019 literatures published in Chinese and English before 2024.1.15 were retrieved from four databases including Pubmed, ScienceDirect, Wan Fang and CNKI. Eventually, 73 eligible studies were included in this review, involving HEV detection data of 64,813 samples collecting from 13 kinds of common domestic animals, locating in 28 provinces and municipalities.

HEV antibodies and RNA were detected among 12 and 7 kinds of domestic animals respectively, with the pooled prevalence of 37.94% (95% CI:32.28-43.77) and 7.62% (95% CI: 5.56-9.96) respectively. The prevelance of HEV for swine samples was higher than other species. In addition, the prevalence of HEV among Tibetan swine, cattle and goats were also at a relatively high level. Further subgroup analysis focusing on comprehensive data from swine was conducted. The results showed, the seroprevalence of HEV antibodies gradually decreased over the time of sampling. HEV RNA was detected in various samples, including bile, feces, liver, and serum. The detection rate for fecal samples was the highest, which was 16.60% (95% CI: 12.17-21.55). Further genotyping of HEV RNA was classified. The results warn us about the circulation of genotype 3 HEV in the eastern region of the Chinese mainland.

The results collected from the included studies provided valuable data on HEV prevalence across various species, and the characteristics, trends, and potential influencing factors were fully discussed. This review provides public health professionals, policymakers, and researchers with comprehensive and up-to-date research data on zoonotic HEV.

Hepatitis E Virus (HEV) is a globally widespread pathogen that causes acute hepatitis infection. Beyond hepatic pathogenesis, HEV has been proven to cause several extrahepatic manifestations, such as neurological, renal, and hematological manifestations. It was also associated with mortality in pregnant females. Several studies have investigated the impact of HEV on the male reproductive system; however, the available data are limited and conflicting. Assessment of the patients' ejaculates/semen samples revealed that HEV particles are excreted in these fluids in cases of chronic infection but not acute infection. The excreted HEV particles are infectious to in vivo animal models and in vitro cell culture. However, the effect of HEV infection on male infertility is not confirmed. One study including human samples showed male infertility associated with HEV genotype 4 infection. Studies of HEV infection in animal models such as pigs, gerbils, and mice showed that HEV infection caused distortion on the testes, damage of the blood-testis barrier, and induction of inflammatory responses leading to abnormalities in the sperm. The excretion of HEV in the semen fluids raises concerns about HEV transmission via sexual transmission. However, all available data do not confirm the transmission of HEV through sexual intercourse. This review aims to summarize and critically assess the available studies investigating the influence of different HEV genotypes on the male reproductive system, providing insights into whether HEV contributes to reproductive impairment in men.

HEV infection has become a global health concern. The study of HEV pathogenicity has been hindered by the lack of a suitable in vitro culture system. In the present research, we systematic demonstration of efficient replication of swine GT4 HEV in A549 cells, Huh-7 cells, and HepG2/C3A cell lines. The results of the immunofluorescence assay and immunofluorescence confocal assay showed that swine GT4 HEV is efficiently replicated in three cell lines at 72 h postinoculation. Meanwhile, we also detected the virus titer quantified were increased at 2-, 6,- and 11-days postinoculation. Moreover, we successfully observed HEV virus particles in the cell suspension at 6 days postinoculation. This finding holds significance for advancing in vitro HEV studies.

Viruses are the most common congenital infections in humans and an important cause of foetal malformations, neonatal morbidity, and mortality. The effects of these infections, which are transmitted in utero (transplacentally), during childbirth or in the puerperium depend on the timing of the infections. These vary from miscarriages (usually with infections in very early pregnancy), congenital malformations (when the infections occur during organogenesis) and morbidity (with infections occurring late in pregnancy, during childbirth or after delivery). The most common of these viruses are cytomegalovirus, hepatitis, herpes simplex type-2, parvovirus B19, rubella, varicella zoster and zika viruses. There are currently very few efficacious antiviral agents licensed for use in pregnancy. For most of these infections, therefore, prevention is mainly by vaccination (where there is a vaccine). The administration of immunoglobulins to those exposed to the virus to offer passive immunity or appropriate measures to avoid being infected would be options to minimise the infections and their consequences. In this review, we discuss some of the congenital and perinatal infections and their consequences on both the mother and fetus and their management focusing mainly on prevention.

Hepatitis E virus (HEV) is an emerging zoonotic pathogen that exhibits great host diversity. The primary means of transmission of the virus in low- and middle-income countries is contaminated water, often due to a lack of access to proper sanitation, which leads to faecal contamination of water sources. Environmental surveillance is an important tool that can be used to monitor virus circulation and as an early warning system for outbreaks. This study was conducted to determine the prevalence and genetic diversity of HEV in wastewater, surface water (rivers and standpipe/ablution water), and effluent from a piggery in South Africa. A total of 536 water samples were screened for HEV using real-time reverse transcription-polymerase chain reaction. Overall, 21.8% (117/536) of the wastewater, river, and ablution water samples tested positive for HEV, whereas 74.4% (29/39) of the samples from the piggery tested positive. Genotyping revealed sequences belonging to HEV genotypes 3 (98%, 53/54) and 4 (2%, 1/54), with subtypes 3c, 3f, and 4b being identified.

The zoonotic transmission of hepatitis E virus (HEV) genotypes 3 (HEV-3) and 4 (HEV-4), and rabbit HEV (HEV-3ra) has been documented. Vaccination against HEV infection depends on the capsid (open reading frame 2, ORF2) protein, which is highly immunogenic and elicits effective virus-neutralizing antibodies. Escherichia coli (E. coli) is utilized as an effective system for producing HEV-like particles (VLPs). However, research on the production of ORF2 proteins from these HEV genotypes in E. coli to form VLPs has been modest. In this study, we constructed 21 recombinant plasmids expressing various N-terminally and C-terminally truncated HEV ORF2 proteins for HEV-3, HEV-3ra, and HEV-4 in E. coli. We successfully obtained nine HEV-3, two HEV-3ra, and ten HEV-4 ORF2 proteins, which were primarily localized in inclusion bodies. These proteins were solubilized in 4 M urea, filtered, and subjected to gel filtration. Results revealed that six HEV-3, one HEV-3ra, and two HEV-4 truncated proteins could assemble into VLPs. The purified VLPs displayed molecular weights ranging from 27.1 to 63.4 kDa and demonstrated high purity (74.7-95.3%), as assessed by bioanalyzer, with yields of 13.9-89.6 mg per 100 mL of TB medium. Immunoelectron microscopy confirmed the origin of these VLPs from HEV ORF2. Antigenicity testing indicated that these VLPs possess characteristic HEV antigenicity. Evaluation of immunogenicity in Balb/cAJcl mice revealed robust anti-HEV IgG responses, highlighting the potential of these VLPs as immunogens. These findings suggest that the generated HEV VLPs of different genotypes could serve as valuable tools for HEV research and vaccine development.

Zoonoses are responsible for many of all emerging infectious diseases as well as for those already established. Rocahepevirus ratti is a rat-originated virus related to the hepatitis E virus (Paslahepevirus balayani) but highly divergent genetically from this, with a high cross-species infection potential and zoonotic transmission. It can infect humans, leading to acute hepatitis, and is primarily transmitted through the consumption of contaminated water. Rocahepevirus ratti was first discovered in Germany in 2010. The first human case was described in 2017 in Hong Kong in an immune-compromised patient. The first case of chronic infection with Rocahepevirus ratti was described in 2023. A meta-analysis based on 38 studies published between 2000 and 2023 identified 21 cases in humans described up to this date and 489 infections in different animals. Raising awareness regarding this virus is essential, as there are probably many cases that remain undiagnosed, and the virus even has the ability to produce chronic infections in selected patients.

The hepatitis E virus (HEV) is a major cause of acute viral hepatitis worldwide. HEV is classified into eight genotypes, labeled HEV-1 through HEV-8. Genotypes 1 and 2 exclusively infect humans, while genotypes 3, 4, and 7 can infect both humans and animals. In contrast, genotypes 5, 6, and 8 are restricted to infecting animals. While most individuals with a strong immune system experience a self-limiting infection, those who are immunosuppressed may develop chronic hepatitis. Pregnant women are particularly vulnerable to severe illness and mortality due to HEV infection. In addition to liver-related complications, HEV can also cause extrahepatic manifestations, including neurological disorders. The immune response is vital in determining the outcome of HEV infection. Deficiencies in T cells, NK cells, and antibody responses are linked to poor prognosis. Interestingly, HEV itself contains microRNAs that regulate its replication and modify the host's antiviral response. Diagnosis of HEV infection involves the detection of HEV RNA and anti-HEV IgM/IgG antibodies. Supportive care is the mainstay of treatment for acute infection, while chronic HEV infection may be cleared with the use of ribavirin and pegylated interferon. Prevention remains the best approach against HEV, focusing on sanitation infrastructure improvements and vaccination, with one vaccine already licensed in China. This comprehensive review provides insights into the spread, genotypes, prevalence, and clinical effects of HEV. Furthermore, it emphasizes the need for further research and attention to HEV, particularly in cases of acute hepatitis, especially among solid-organ transplant recipients.

The hepatitis E virus is a serious health concern worldwide, with 20 million cases each year. Growing numbers of autochthonous HEV infections in industrialized nations are brought on via the zoonotic transmission of HEV genotypes 3 and 4. Pigs and wild boars are the main animal reservoirs of HEV and play the primary role in HEV transmission. Consumption of raw or undercooked pork meat and close contact with infected animals are the most common causes of hepatitis E infection in industrialized countries. However, during the past few years, mounting data describing HEV distribution has led experts to believe that additional animals, particularly domestic ruminant species (cow, goat, sheep, deer, buffalo, and yak), may also play a role in the spreading of HEV. Up to now, there have not been enough studies focused on HEV infections associated with animal milk and the impact that they could have on the epidemiology of HEV. This critical analysis discusses the role of domestic ruminants in zoonotic HEV transmissions. More specifically, we focus on concerns related to milk safety, the role of mixed farming in cross-species HEV infections, and what potential consequences these may have on public health.

Hepatitis E virus (HEV) is one of the leading causes of acute viral hepatitis worldwide. Although most of HEV infections are asymptomatic, some patients will develop the symptoms, especially pregnant women, the elderly, and patients with preexisting liver diseases, who often experience anorexia, nausea, vomiting, malaise, abdominal pain, and jaundice. HEV infection may become chronic in immunosuppressed individuals. In addition, HEV infection can also cause several extrahepatic manifestations. HEV exists in a wide range of hosts in nature and can be transmitted across species. Hence, animals susceptible to HEV can be used as models. The establishment of animal models is of great significance for studying HEV transmission, clinical symptoms, extrahepatic manifestations, and therapeutic strategies, which will help us understand the pathogenesis, prevention, and treatment of hepatitis E. This review summarized the animal models of HEV, including pigs, monkeys, rabbits, mice, rats, and other animals. For each animal species, we provided a concise summary of the HEV genotypes that they can be infected with, the cross-species transmission pathways, as well as their role in studying extrahepatic manifestations, prevention, and treatment of HEV infection. The advantages and disadvantages of these animal models were also emphasized. This review offers new perspectives to enhance the current understanding of the research landscape surrounding HEV animal models.

The smallest open reading frame (ORF) encoded protein ORF3 of hepatitis E virus (HEV), recently, has been demonstrated to perform multiple functions besides accessory roles. ORF3 could act as a target for vaccine against HEV infections. The IDR (intrinsically disordered region); IDP (ID protein)/IDPR (ID protein region), plays critical role in various regulatory functions of viruses. The dark proteome of HEV-ORF3 protein including its structure and function was systematically examined by computer predictors to explicate its role in viral pathogenesis and drug resistance beyond its functions as accessory viral protein. Amino acid distribution showed ORF3 enrichment with disorder-promoting residues (Ala, Pro, Ser, Gly) while deficiency in order-promoting residues (Asn, Ile, Phe, Tyr and Trp). Initial investigation revealed ORF3 as IDP (entirely disordered protein) or IDPR (proteins consisting of IDRs with structured globular domains). Structural examination revealed preponderance of disordered regions interpreting ORF3 as moderately/highly disordered protein. Further disorder predictors categorized ORF3 as highly disordered protein/IDP. Identified sites and associated-crucial molecular functions revealed ORF3 involvement in diverse biological processes, substantiating them as targets of regulation. As ORF3 functions are yet to completely explored, thus, data on its disorderness could help in elucidating its disorder related functions.

Hepatitis E virus (HEV) infection is a common cause of acute viral hepatitis in tropical regions. In Brazil, HEV G3 is the only genotype detected to date. Reports on HEV prevalence are heterogeneous. We aimed to compare the prevalence of anti-HEV among three populations living in the Brazilian Amazon basin. Two cross-sectional studies were conducted in urban, rural, and Yanomami indigenous areas. Plasma samples from 428 indigenous and 383 non-indigenous subjects were tested for anti-HEV IgG using enzyme-linked immunosorbent assays. The overall prevalence of anti-HEV was 6.8% (95%CI: 5.25-8.72), with 2.8% (12/428) found in the Yanomami areas, 3% (3/101) in an urban area, and 14.2% (40/282) in a rural area. Multivariate logistic analysis indicated that patients aged 31-45 years or ≥46 years are more likely to present anti-HEV positivity, with a respective aOR of 2.76 (95%CI: 1.09-7.5) and 4.27 (95%CI: 1.58-12.35). Furthermore, residence in a rural area (aOR: 7.67; 95%CI: 2.50-33.67) represents a relevant risk factor for HEV infection. Additional studies detecting HEV RNA in fecal samples from both humans and potential animal reservoirs are necessary to comprehensively identify risk factors associated with HEV exposure.

Hepatitis E virus (HEV), an emerging zoonotic pathogen, poses a significant public health concern worldwide. Recently, rat HEV (Rocahepevirus ratti genotype C1; HEV-C1) has been reported to cause zoonotic infections and hepatitis in humans. Human infections with HEV-C1 are considered to be underestimated worldwide due to limited knowledge of transmission routes, genome epidemiology, and the risk assessment of zoonosis associated with these viruses. A total of 186 wild Norway rats (Rattus norvegicus) were collected from the Republic of Korea (ROK) between 2011 and 2021. The prevalence of HEV-C1 RNA was 8 of 180 (4.4%) by reverse-transcription polymerase chain reaction. We first reported three nearly whole-genome sequences of HEV-C1 newly acquired from urban rats in the ROK. Phylogenetic analysis demonstrated that Korea-indigenous HEV-C1 formed an independent genetic group with those derived from R. norvegicus rats in other countries, indicating geographical and genetic diversity. Our findings provide critical insights into the molecular prevalence, genome epidemiology, and zoonotic potential of Rocahepevirus. This report raises awareness of the presence of Rocahepevirus-related hepatitis E among physicians in the ROK.

Enteric viruses are the major cause of gastroenteritis and enteric hepatitis worldwide, but in some areas like Saudi Arabia, little is known about their presence in water sources. The available information from clinical samples is not enough to figure out their actual prevalence. The aim of this study was to gather information for the first time in Saudi Arabia on the presence of the Norovirus (NoV) genogroup GI and GII, hepatitis A virus (HAV), and hepatitis E virus (HEV) in water. For this purpose, thirteen monthly samples were collected from Lake Wadi Hanifa and surrounding wells from December 2014 to November 2015. Viruses were detected and quantified using real-time RT-qPCR. Despite HEV findings being anecdotic, our results highlight interesting behaviors of the other viruses. There was a higher prevalence of noroviruses in Wadi Hanifa samples than in well water samples (46.43% vs. 12.5% of NoV GI; 66.67% vs. 8.33% of NoV GII). On the contrary, similar levels of HAV positivity were observed (40.48% in surface water vs. 43.06% in well water). Also, a strong influence of flooding events on HAV and NoV GI occurrence was observed in both surface and well water samples, with NoV GII apparently not affected.

Hepatitis E virus (HEV) infection has been demonstrated in various animal species; those recognized as potential zoonotic reservoirs pose a considerable risk to public health. In Brazil, HEV-3 is the only genotype identified in humans and swine nationwide, in a colony-breeding cynomolgus monkey and, recently, in bovines and capybara. There is no information regarding HEV exposure in the equine population in Brazil. This study aimed to investigate anti-HEV antibodies and viral RNA in serum samples from horses slaughtered for meat export and those bred for sport/reproduction purposes. We used a commercially available ELISA kit modified to detect species-specific anti-HEV, using an anti-horse IgG-peroxidase conjugate and evaluating different cutoff formulas and assay precision. Serum samples (n = 257) were tested for anti-HEV IgG and HEV RNA by nested RT-PCR and RT-qPCR. The overall anti-HEV seroprevalence was 26.5% (68/257) without the detection of HEV RNA. Most municipalities (53.3%) and farms (58.8%) had positive horses. Animals slaughtered for human consumption had higher risk of HEV exposure (45.5%) than those bred for sports or reproduction (6.4%) (p < 0.0001). The statistical analysis revealed sex and breeding system as possible risk-associated factors. The first serological evidence of HEV circulation in Brazilian equines reinforces the need for the surveillance of HEV host expansion in a one-health approach.

Hepatitis E virus (HEV) is an emerging cause of viral hepatitis and pigs are considered a reservoir for the virus. HEV genotype 3 (HEV-3) has been reported in pigs, environmental matrices, and sporadic human cases in Argentina. We aimed to investigate HEV circulation in pigs from central Argentina and to assess the virus presence in pork meat and food products. Four types of samples obtained or derived from pigs collected in Córdoba province (Argentina) between 2019 and 2022, were tested: 276 serum samples were analyzed for anti-HEV antibody detection; stool (n = 20), pork meat (n = 71), and salami (n = 76) samples were studied for RNA-HEV detection, followed by sequencing and phylogenetic analyses. The positivity rate for anti-HEV antibodies was 80.1% (221/276). Eleven fecal samples (11/20) tested positive for RNA-HEV, from animals under 120 days of age. Three samples could be sequenced, and phylogenetic analyses revealed that they belonged to HEV-3 clade abchijklm, clustering close to strains previously detected in wastewater from Córdoba. None of the muscle meat or salami samples tested positive. A high HEV circulation in pigs was found, showing that these animals may play a significant role in the viral maintenance in the region, becoming a potential risk to the exposed population. Despite not detecting RNA-HEV in pork meat and salami in our study, we cannot rule out the possibility of foodborne transmission in Córdoba province.

Hepatitis E virus (HEV) is a leading cause of acute hepatitis and can cause chronic infections in immunocompromised patients. Although HEV infections can be treated with ribavirin, antiviral efficacy is hampered by resistance mutations, normally detected by virus sequencing.

High-throughput sequencing (HTS) allows for cost-effective complete viral genome sequencing. This enables the discovery and delineation of new subtypes, and revised the recognition of quasispecies and putative resistance mutations. However, HTS is challenged by factors including low viral load, sample degradation, high host background, and high viral diversity.

We apply complete genome sequencing strategies for HEV, including a targeted enrichment approach. These approaches were used to investigate sequence diversity in HEV RNA-positive animal and human samples and intra-host diversity in a chronically infected patient.

Here, we describe the identification of potential novel subtypes in a blood donation (genotype 3) and in an ancient livestock sample (genotype 7). In a chronically infected patient, we successfully investigated intra-host virus diversity, including the presence of ribavirin resistance mutations. Furthermore, we found convincing evidence for HEV compartmentalization, including the central nervous system, in this patient.

Targeted enrichment of viral sequences enables the generation of complete genome sequences from a variety of difficult sample materials. Moreover, it enables the generation of greater sequence coverage allowing more advanced analyses. This is key for a better understanding of virus diversity. Investigation of existing ribavirin resistance, in the context of minorities or compartmentalization, may be critical in treatment strategies of HEV patients.

Hepatitis E virus (HEV) is a zoonotic foodborne virus with an annual infection prevalence of 20 million human cases, which seriously affects public health and economic development in both developed and developing countries. To better understand the epidemiology of HEV in Central Portugal, a cross-sectional study was conducted from 2016 to 2023 with sera samples from wild ungulates. The seroprevalence and risk factors for HEV seropositivity were evaluated in the present study. Specifically, antibodies against HEV were determined by a commercial enzyme-linked immune-sorbent assay (ELISA). Our results show that in the 650 sera samples collected from 298 wild red deer and 352 wild boars in Portugal, 9.1% red deer and 1.7% wild boar were positive for antibodies to HEV. Regarding age, the seropositivity in juvenile wild ungulates was 1.3%, whereas it was 7.2% in adults. Logistic regression models investigated risk factors for seropositivity. The odds of being seropositive was 3.6 times higher in adults than in juveniles, and the risk was 4.2 times higher in red deer than in wild boar. Both wild ungulate species were exposed to HEV. The higher seroprevalence in red deer suggests that this species may make a major contribution to the ecology of HEV in Central Portugal. Further research is needed to understand how wildlife affects the epidemiology of HEV infections in Portugal.

Hepatitis E virus (HEV) is a zoonotic pathogen that is widespread worldwide. At present, most enzyme-linked immunosorbent assay (ELISA) kits only detect antibodies against human HEV. In this study, a nanobody-horseradish peroxidase (HRP) fusion protein-based competitive ELISA (cELISA) with more convenience and spectral characteristics for HEV antibody detection was developed and used to detect HEV IgG in various species. First, 6 anti-swine HEV capsid protein nanobodies were screened using phage display technology from an immunized Bactrian camel. Then, HEV-Nb67-HRP fusions were expressed and used as a probe for developing a cELISA. The cutoff value of the cELISA was 17.8%, and there was no cross-reaction with other anti-swine virus antibodies, suggesting that the cELISA had good specificity. The intra-assay and interassay coefficients of variation (CVs) were 1.33 to 5.06% and 1.52 to 6.84%, respectively. The cELISA and Western blot showed a higher coincidence rate (97.14%, kappa value = 0.927) than cELISA and indirect ELISA (95.00%, kappa value = 0.876) in clinical swine serum samples. Finally, the seroprevalence of HEV IgG in humans, pigs, rabbits, cows, and goats was 30.67%, 19.26%, 8.75%, 27.59%, and 18.08%, respectively, suggesting that cELISA may have a broader scale for mammalian HEV antibody detection. These results suggest that the newly developed cELISA was rapid, low-cost, reliable, and useful for the serological evaluation of current HEV. IMPORTANCE HEV is thought to be a zoonotic infection and is widespread worldwide; it is beneficial to establish a more convenient and spectral method for HEV antibody detection. In this study, a convenient, time-saving, reproducible, highly sensitive, specific, and novel nanobody-based cELISA was developed and can be used to detect IgG antibodies against mammalian HEV. It provides a new technique for serological evaluation and ELISA-based diagnosis of HEV infection.

In recent years, hepatitis E virus (HEV) infection has been found to be widespread among different animal species worldwide. In Bulgaria, high HEV seropositivity was found among pigs (60.3%), wild boars (40.8%), and East Balkan swine (82.5%). The aim of the present study was to establish the seroprevalence of HEV among dogs, cats, horses, cattle, sheep, and goats in Bulgaria. In total, 720 serum samples from six animal species were randomly collected: dogs-90 samples; cats-90; horses-180; cattle-180; sheep-90; and goats-90. The serum samples were collected from seven districts of the country: Burgas, Kardzhali, Pazardzhik, Plovdiv, Sliven, Smolyan, and Stara Zagora. The animal serum samples were tested for HEV antibodies using the commercial Wantai HEV-Ab ELISA kit (Beijing, China). The overall HEV seroprevalence among different animal species from Bulgaria was as follows: dogs-21.1%; cats-17.7%; horses-8.3%; cattle-7.7%; sheep-32.2%; and goats-24.4%. We found the lowest overall HEV seropositivity in Plovdiv district (6.2%; 4/64; p = 0.203) and Smolyan district (8.8%; 4/45; p = 0.129), vs. the highest in Pazardzhik district (21.6%; 29/134; p = 0.024) and Burgas district (28.8%; 26/90; p = 0.062). To the best of our knowledge, this is the first serological evidence of HEV infection in dogs, cats, horses, cattle, sheep, and goats from Bulgaria. We found high HEV seropositivity in small ruminants (sheep and goats), moderate seropositivity in pets (dogs and cats), and a low level of seropositivity in large animals (horses and cattle). Previous Bulgarian studies and the results of this research show that HEV infection is widespread among animals in our country. In this regard, the Bulgarian health authorities must carry out increased surveillance and control of HEV infection among animals in Bulgaria.

Hepatitis E virus (HEV) is one of the leading causes of acute viral hepatitis. Transmission of HEV mainly occurs via the fecal-oral route (ingesting contaminated water or food) or by contact with infected animals and their raw meat products. Some animals, such as pigs, wild boars, sheep, goats, rabbits, camels, rats, etc., are natural reservoirs of HEV, which places people in close contact with them at increased risk of HEV disease. Although hepatitis E is a self-limiting infection, it could also lead to severe illness, particularly among pregnant women, or chronic infection in immunocompromised people. A growing number of studies point out that HEV can be classified as a re-emerging virus in developed countries. Preventative efforts are needed to reduce the incidence of acute and chronic hepatitis E in non-endemic and endemic countries. There is a recombinant HEV vaccine, but it is approved for use and commercially available only in China and Pakistan. However, further studies are needed to demonstrate the necessity of applying a preventive vaccine and to create conditions for reducing the spread of HEV. This review emphasizes the hepatitis E virus and its importance for public health in Europe, the methods of virus transmission and treatment, and summarizes the latest studies on HEV vaccine development.

The public health significance of hepatitis E is very important [...].

Paslahepevirus balayani (hepatitis E virus [HEV]) is the causative agent of hepatitis E, a worldwide zoonosis involving a wide range of hosts among domestic and wild animals. This species is characterized by a great genomic heterogeneity and includes eight genotypes, HEV-1 to HEV-8. The HEV-3 genotype is one of the most common types circulating in Italy in humans and Suidae. Although domestic and wild Sus scrofa and deer (Cervidae) are recognized as the main reservoirs of HEV, several other wild species are potential carriers. A total of 228 liver samples were collected from nonungulate wild animals, found dead, in the framework of the regional passive surveillance program in Umbria and Marche regions (central Italy) during 2018-20. These were tested using real-time reverse-transcriptase PCR (RT-PCR) for detection of RNA of HEV-1 to HEV-4 and confirmed by nested RT-PCR assay. One of the 11 samples collected from crested porcupines (Hystrix cristata) tested positive for the presence of HEV RNA; all other samples were negative. Sequence analysis based on the full-length genome revealed that this isolate, 49434/UM/2018 (accession no. OL658617), belongs to the HEV-3e subtype. These findings suggest a potential role of crested porcupines as a carrier of HEV infection.

Hepatitis E virus (HEV) circulation in humans and swine has been extensively studied in South America over the last two decades. Nevertheless, only 2.1% of reported HEV strains are available as complete genome sequences. Therefore, many clinical, epidemiological, and evolutionary aspects of circulating HEV in the continent still need to be clarified. Here, we conducted a retrospective evolutionary analysis of one human case and six swine HEV strains previously reported in northeastern, southern, and southeastern Brazil. We obtained two complete and four nearly complete genomic sequences. Evolutionary analysis comparing the whole genomic and capsid gene sequences revealed high genetic variability. This included the circulation of at least one unrecognized unique South American subtype. Our results corroborate that sequencing the whole capsid gene could be used as an alternative for HEV subtype assignment in the absence of complete genomic sequences. Moreover, our results substantiate the evidence for zoonotic transmission by comparing a larger genomic fragment recovered from the sample of the autochthonous human hepatitis E case. Further studies should continuously investigate HEV genetic diversity and zoonotic transmission of HEV in South America.

Hepatitis E virus (HEV) represents a major cause of acute hepatitis and is considered an emerging public health problem around the world. In the Middle East's and Africa's arid regions, where camels frequently interact with human populations and camel-derived food products are a component of the food chain, camel-borne zoonotic HEV infection is a potential threat. To date, no review paper has been published on HEV in camels. As such, the purpose of the current work is to provide a scientific review of the identification of HEV genotypes seven and eight in camels worldwide to have a better understanding of the current status of this topic and to identify gaps in the current knowledge. Searches were carried out in the electronic databases PubMed, Mendeley, Web of Science, and Scopus, including studies published until 31 December 2022 (n = 435). Once the databases were checked for duplicate papers (n = 307), the exclusion criteria were applied to remove any research that was not relevant (n = 118). As a result, only 10 papers were found to be eligible for the study. Additionally, in eight of the ten studies, the rates of HEV infection were found to be between 0.6% and 2.2% in both stool and serum samples. Furthermore, four studies detected HEV genotype seven in dromedary camels, and two studies have shown HEV genotype eight in Bactrian camels. Interestingly, these genotypes were recently reported in camels from the Middle East and China, where one human infection with HEV genotype seven has been associated with the consumption of contaminated camel meat and milk. In conclusion, more research will be needed to determine the prevalence of HEV infection in camels around the world as well as the risk of foodborne transmission of contaminated camel products. As camels are utility animals in several countries, HEV in these animals may pose a potential risk to public health.

Hepatitis A and hepatitis E are relatively common causes of liver disease. Both viruses are mainly transmitted through the faecal-oral route and, consequently, most outbreaks occur in countries with poor sanitation. An important role of the immune response as the driver of liver injury is also shared by the two pathogens. For both the hepatitis A (HAV) and hepatitis E (HEV) viruses, the clinical manifestations of infection mainly consist of an acute disease with mild liver injury, which results in clinical and laboratory alterations that are self-limiting in most cases. However, severe acute disease or chronic, long-lasting manifestations may occur in vulnerable patients, such as pregnant women, immunocompromised individuals or those with pre-existing liver disease. Specifically, HAV infection rarely results in fulminant hepatitis, prolonged cholestasis, relapsing hepatitis and possibly autoimmune hepatitis triggered by the viral infection. Less common manifestations of HEV include extrahepatic disease, acute liver failure and chronic HEV infection with persistent viraemia. In this paper, we conduct a non-systematic review of the available literature to provide a comprehensive understanding of the state of the art. Treatment mainly consists of supportive measures, while the available evidence for aetiological treatment and additional agents in severe disease is limited in quantity and quality. However, several therapeutic approaches have been attempted: for HAV infection, corticosteroid therapy has shown outcome improvement, and molecules, such as AZD 1480, zinc chloride and heme oxygenase-1, have demonstrated a reduction in viral replication in vitro. As for HEV infection, therapeutic options mainly rely on the use of ribavirin, and some studies utilising pegylated interferon-alpha have shown conflicting results. While a vaccine for HAV is already available and has led to a significant reduction in the prevalence of the disease, several vaccines for HEV are currently being developed, with some already available in China, showing promising results.

Autochthonous hepatitis E (HEV) cases have been increasingly recognized and reported in Europe, caused predominantly by the zoonotic HEV genotype 3. The clinical picture is highly variable, from asymptomatic to acute severe or prolonged hepatitis in immunocompromised patients. The main route of transmission to humans in Europe is the ingestion of undercooked pork meat. Transfusion-transmitted HEV infections have also been reported. The aim of the study was to determine the HEV epidemiology and risk in the Finnish blood donor population. A total of 23,137 samples from Finnish blood donors were screened for HEV RNA from individual samples and 1012 samples for HEV antibodies. Additionally, laboratory-confirmed hepatitis E cases in 2016-2022 were extracted from national surveillance data. The HEV RNA prevalence data was used to estimate the risk of transfusion transmission of HEV in the Finnish blood transfusion setting. Four HEV RNA-positive were found, resulting in 1:5784 (0.02%) RNA prevalence. All HEV RNA-positive samples were IgM-negative, and genotyped samples represented genotype HEV 3c. HEV IgG seroprevalence was 7.4%. From the HEV RNA rate found in this study and data on blood component usage in Finland in 2020, the risk estimate for a severe transfusion-transmitted HEV infection is 1:1,377,000 components or one in every 6-7 years. In conclusion, the results indicate that the risk of transfusion-transmitted HEV (HEV TTI) in Finland is low. However, continuous follow-up of the HEV epidemiology in relation to the transfusion risk landscape in Finland is necessary, as well as promoting awareness in the medical community of the small risk for HEV TTI, especially for immunocompromised patients.

Genotype 1 hepatitis E virus (HEV-1), unlike other genotypes of HEV, has a unique small open reading frame known as ORF4 whose function is not yet known. ORF4 is located in an out-framed manner in the middle of ORF1, which encodes putative 90 to 158 amino acids depending on the strains. To explore the role of ORF4 in HEV-1 replication and infection, we cloned the complete genome of wild-type HEV-1 downstream of a T7 RNA polymerase promoter, and the following ORF4 mutant constructs were prepared: the first construct had TTG instead of the initiation codon ATG (A2836T), introducing an M→L mutation in ORF4 and a D→V mutation in ORF1. The second construct had ACG instead of the ATG codon (T2837C), introducing an M→T mutation in ORF4. The third construct had ACG instead of the second in-frame ATG codon (T2885C), introducing an M→T mutation in ORF4. The fourth construct contained two mutations (T2837C and T2885C) accompanying two M→T mutations in ORF4. For the latter three constructs, the accompanied mutations introduced in ORF1 were all synonymous changes. The capped entire genomic RNAs were generated by in vitro transcription and used to transfect PLC/PRF/5 cells. Three mRNAs containing synonymous mutations in ORF1, i.e., T2837C^RNA, T2885C^RNA, and T2837C/T2885C^RNA, replicated normally in PLC/PRF/5 cells and generated infectious viruses that successfully infected Mongolian gerbils as the wild-type HEV-1 did. In contrast, the mutant RNA, i.e., A2836T^RNA, accompanying an amino acid change (D937V) in ORF1 generated infectious viruses upon transfection, but they replicated slower than the wild-type HEV-1 and failed to infect Mongolian gerbils. No putative viral protein(s) derived from ORF4 were detected in the wild-type HEV-1- as well as the mutant virus-infected PLC/PRF/5 cells by Western blot analysis using a high-titer anti-HEV-1 IgG antibody. These results demonstrated that the ORF4-defective HEV-1s had the ability to replicate in the cultured cells, and that these defective viruses had the ability to infect Mongolian gerbils unless the overlapping ORF1 was accompanied by non-synonymous mutation(s), confirming that ORF4 is not essential in the replication and infection of HEV-1.

Hepatitis E virus (HEV) is the cause of a liver disease hepatitis E. The translation product of HEV ORF2 has recently been demonstrated as a protein involved in multiple functions besides performing its major role of a viral capsid. As intrinsically disordered regions (IDRs) are linked to various essential roles in the virus's life cycle, we analyzed the disorder pattern distribution of the retrieved ORF2 protein sequences by employing different online predictors. Our findings might provide some clues on the disorder-based functions of ORF2 protein that possibly help us in understanding its behavior other than as a HEV capsid protein.

The modeled three dimensional (3D) structures of ORF2 showed the predominance of random coils or unstructured regions in addition to major secondary structure components (alpha helix and beta strand). After initial scrutinization, the predictors VLXT and VSL2 predicted ORF2 as a highly disordered protein while the predictors VL3 and DISOPRED3 predicted ORF2 as a moderately disordered protein, thus categorizing HEV-ORF2 into IDP (intrinsically disordered protein) or IDPR (intrinsically disordered protein region) respectively. Thus, our initial predicted disorderness in ORF2 protein 3D structures was in excellent agreement with their predicted disorder distribution patterns (evaluated through different predictors). The abundance of MoRFs (disorder-based protein binding sites) in ORF2 was observed that signified their interaction with binding partners which might further assist in viral infection. As IDPs/IDPRs are targets of regulation, we carried out the phosphorylation analysis to reveal the presence of post-translationally modified sites. Prevalence of several disordered-based phosphorylation sites further signified the involvement of ORF2 in diverse and significant biological processes. Furthermore, ORF2 structure-associated functions revealed its involvement in several crucial functions and biological processes like binding and catalytic activities.

The results predicted ORF2 as a protein with multiple functions besides its role as a capsid protein. Moreover, the occurrence of IDPR/IDP in ORF2 protein suggests that its disordered region might serve as novel drug targets via functioning as potential interacting domains. Our data collectively might provide significant implication in HEV vaccine search as disorderness in viral proteins is related to mechanisms involved in immune evasion.

Hepatitis E virus (HEV) has emerged as a public health concern in Brazil. From the first identification and characterization of porcine and human HEV-3 strains in the 2000s, new HEV subtypes have been identified from animal, human, and environmental isolates. As new potential animal reservoirs have emerged, there is a need to compile evidence on the zoonotic dissemination of the virus in animal hosts and the environment. The increasing amount of seroprevalence data on sampled and randomly selected populations must be systematically retrieved, interpreted, and considered under the One Health concept. This review focused on HEV seroprevalence data in distinct animal reservoirs and human populations reported in the last two decades. Furthermore, the expertise with experimental infection models using non-human primates may provide new insights into HEV pathogenesis, prevention, and environmental surveillance.

The Hepatitis E virus (HEV) is a common cause of viral hepatitis worldwide. Little is known about the seroprevalence of HEV in the general population of Saudi Arabia.

A community-based cross-sectional HEV seroprevalence study was conducted in Makkah, Saudi Arabia. Anti-HEV IgG antibodies were detected in sera using an in-house ELISA. The frequency of HEV sageerology and its correlation with demographic, and environmental factors were evaluated.

Enrollment consisted of 1329 individuals, ages ranged from 8 to 88 years, the mean age was 30.17 years, the median age was 28yrs, and the male: female ratio was 1.15. The overall seroprevalence was 23.8% (316/1329). Males had significantly higher seroprevalence than females (66.1 vs. 33.9%; p < 0.001). Seroprevalence had significant correlations with age, occupation, and lack of regular water supply and housing conditions.

This is the first HEV community-based seroprevalence study from Saudi Arabia. Results show that the HEV is endemic in Makkah and affects all age groups and occupations. HEV affects more males than females and those living in crowded accommodations without a regular supply of water. Further studies are required across all regions of Saudi Arabia to determine the country's seroprevalence of active or past infection using tests for HEV IgG, HEV IgM antibodies and/or HEV RNA and underlying determinants of transmission.

The majority of Hepatitis E Virus (HEV)-related studies are carried out in adults whereas information about HEV seroprevalence, clinical disease manifestation, molecular epidemiology, and transmission patterns in children is limited. To estimate HEV seroprevalence among scholar children living in an urban setting and to analyze risk factors for an infection, we invited children aged 5-18 years from Bogotá (Colombia) for a cross-sectional survey. We collected self-reported data on demographics, social, clinical, and exposure variables in a structured interview. Venous blood samples were analyzed with two commercially available ELISAs for HEV-specific IgG antibodies. Among the 263 participants, we found three HEV IgG-reactive samples (1.1%) using both assays. We additionally characterized the samples for HEV IgM using a commercially available IgM ELISA and for HEV RNA. Here, we found one IgM-reactive sample, which was also reactive for IgG. In contrast, none of the IgM- and IgG-reactive sera samples showed detectable RNA levels indicating HEV exposure had not been recently. All participants reported access to drinking water and sanitary systems in their households and frequent hand washing routines (76-88%). Eighty percent of children reported no direct contact with pigs, but occasional pork consumption was common (90%). In contrast to the majority of studies performed in Colombian adults, we found a low unadjusted HEV seroprevalence of 1.1% (95% CI: 0.3-3.6%) for both HEV IgG ELISAs in our study population. While the majority of participants reported pork consumption, we speculate in the absence of viral RNA for genotyping in the affected individuals, that existing access to drinking water and sanitary systems within our study group contribute to the low HEV seroprevalence.

Hepatitis E virus (HEV) is an emerging zoonotic pathogen associated with relevant public health issues. The aim of this study was to investigate HEV presence in free-living capybaras inhabiting urban parks in São Paulo state, Brazil. Molecular characterization of HEV positive samples was undertaken to elucidate the genetic diversity of the virus in these animals. A total of 337 fecal samples were screened for HEV using RT-qPCR and further confirmed by conventional nested RT-PCR. HEV genotype and subtype were determined using Sanger and next-generation sequencing. HEV was detected in one specimen (0.3%) and assigned as HEV-3f. The IAL-HEV_921 HEV-3f strain showed a close relationship to European swine, wild boar and human strains (90.7-93.2% nt), suggesting an interspecies transmission. Molecular epidemiology of HEV is poorly investigated in Brazil; subtype 3f has been reported in swine. This is the first report of HEV detected in capybara stool samples worldwide.

Viral hepatitis is an infection of human hepatocytes resulting in liver damage. Dual infection of two hepatotropic viruses affects disease outcomes. The hepatitis A virus (HAV) and hepatitis E virus (HEV) are two enterically transmitted viruses; they are single-stranded RNA viruses and have common modes of transmission. They are transmitted mainly by the fecal-oral route and ingestion of contaminated food, though the HAV has no animal reservoirs. The HAV and HEV cause acute self-limiting disease; however, the HEV, but not HAV, can progress to chronic and extrahepatic infections. The HAV/HEV dual infection was reported among acute hepatitis patients present in developing countries. The impact of the HAV/HEV on the prognosis for acute hepatitis is not completely understood. Studies showed that the HAV/HEV dual infection increased abnormalities in the liver leading to fulminant hepatic failure (FHF) with a higher mortality rate compared to infection with a single virus. On the other hand, other reports showed that the clinical symptoms of the HAV/HEV dual infection were comparable to symptoms associated with the HAV or HEV monoinfection. This review highlights the modes of transmission, the prevalence of the HAV/HEV dual infection in various countries and among several study subjects, the possible outcomes of this dual infection, potential model systems for studying this dual infection, and methods of prevention of this dual infection and its associated complications.

Hepatitis E virus (HEV) is an important but understudied virus that has been the major cause of acute viral hepatitis worldwide. In recent decades, our understanding of this neglected virus has changed greatly: novel forms of viral proteins and their functions have been discovered; HEV can transmit via blood transfusion and organ transplantation; HEV can infect many animal species and the number is still increasing; HEV can induce chronic hepatitis and extra-hepatic manifestations. However, we are short of effective treatment measures to counter the virus. In this chapter we tend to briefly introduce the puzzles and major knowledge gaps existed in the field of HEV research.

Hepatitis E viruses in the family of Hepeviridae have been classified into 2 genus, 5 species, and 13 genotypes, involving different animal hosts of different habitats. Among all these genotypes, four (genotypes 3, 4, 7, and C1) of them are confirmed zoonotic causing sporadic human diseases, two (genotypes 5 and 8) were likely zoonotic showing experimental animal infections, and the other seven were not zoonotic or unconfirmed. These zoonotic HEV carrying hosts include pig, boar, deer, rabbit, camel, and rat. Taxonomically, all the zoonotic HEVs belong to the genus Orthohepevirus, which include genotypes 3, 4, 5, 7, 8 HEV in the species A and genotype C1 HEV in the species C. In the chapter, information of zoonotic HEV such as swine HEV (genotype 3 and 4), wild boar HEV (genotypes 3-6), rabbit HEV (genotype 3), camel HEV (genotype 7 and 8), and rat HEV (HEV-C1) was provided in detail. At the same time, their prevalence characteristics, transmission route, phylogenetic relationship, and detection technology were discussed. Other animal hosts of HEVs were introduced briefly in the chapter. All these information help peer researchers have basic understanding of zoonotic HEV and adopt reasonable strategy of surveillance and prevention.

Comparative analysis of the genomic sequences of multiple hepatitis E virus (HEV) isolates has revealed extensive genomic diversity among them. Recently, a variety of genetically distinct HEV variants have also been isolated and identified from large numbers of animal species, including birds, rabbits, rats, ferrets, bats, cutthroat trout, and camels, among others. Furthermore, it has been reported that recombination in HEV genomes takes place in animals and in human patients. Also, chronic HEV infection in immunocompromised individuals has revealed the presence of viral strains carrying insertions from human genes. This paper reviews current knowledge on the genomic variability and evolution of HEV.

Since the sequence of hepatitis E virus (HEV) was determined from a patient with enterically transmitted non-A, non-B hepatitis in 1989, similar sequences have been isolated from many different animals, including pigs, wild boars, deer, rabbits, bats, rats, chicken, and trout. All of these sequences have the same genomic organization, which contains open reading frames (ORFs) 1, 2, and 3, although their genomic sequences are variable. Some have proposed that they be classified as new family, Hepeviridae, which would be further divided into different genera and species according to their sequence variability. The size of these virus particles generally ranged from 27 to 34 nm. However, HEV virions produced in cell culture differ in structure from the viruses found in feces. Those from cell culture have a lipid envelope and either lack or have a little ORF3, whereas the viruses isolated from feces lack a lipid envelope but have ORF3 on their surfaces. Surprisingly, most of the secreted ORF2 proteins from both these sources are not associated with HEV RNA.

Hepatitis E virus (HEV) causes infections in humans and a wide range of animal hosts. Wild boar is an important natural reservoir of HEV genotypes 3−6 (HEV-3−HEV-6), but comparative analysis of HEV infections in both feral and farmed wild boars remains limited. In this study, samples from 599 wild boars were collected during 2017−2020, including 121 feral wild boars (collected 121 fecal, 121 serum, and 89 liver samples) and 478 farmed wild boars (collected 478 fecal and 478 serum samples). The presence of anti-HEV IgG antibodies were detected by the HEV-IgG enzyme-linked immunosorbent assay (ELISA) kit. HEV RNA was detected by reverse transcription polymerase chain reaction (RT-PCR), targeting the partial ORF1 genes from fecal and liver samples, and the obtained genes were further genotyped by phylogenetic analysis. The results showed that 76.2% (95% CI 72.1−79.9) of farmed wild boars tested anti-HEV IgG seropositive, higher than that in feral wild boars (42.1%, 95% CI 33.2−51.5, p < 0.001). HEV seropositivity increased with age. Wild boar HEV infection presented a significant geographical difference (p < 0.001), but not between sex (p = 0.656) and age (p = 0.347). HEV RNA in fecal samples was detected in 13 (2.2%, 95% CI 1.2−3.7) out of 599 wild boars: 0.8% (95% CI 0.0−4.5, 1/121) of feral wild boars and 2.5% (95% CI 1.3−4.3, 12/478) of farmed wild boars. Phylogenetic analysis showed that all these viruses belonged to genotype HEV-4, and further grouped into sub-genotypes HEV-4a, HEV-4d, and HEV-4h, of which HEV-4a was first discovered in the wild boar populations in China. Our results suggested that farms could be a setting for amplification of HEV. The risk of HEV zoonotic transmission via rearing and consumption of farmed wild boars should be further assessed.

Though Egypt ranks among the top countries for viral hepatitis and death-related liver disease, Hepatitis E virus (HEV) is a neglected pathogen. Living in villages and rural communities with low sanitation, use of underground well water and contact with animals are the main risk factors for HEV infection. Domestic animals, especially ruminants and their edible products, are one source of infection. Contamination of water by either human or animal stools is the main route of infection. In addition, HEV either alone or in coinfection with other hepatotropic viruses has been recorded in Egyptian blood donors. HEV seropositivity among Egyptian villagers was 60-80%, especially in the first decade of life. Though HEV seropositivity is the highest among Egyptians, HEV infection is not routinely diagnosed in Egyptian hospitals. The initial manifestations of HEV among Egyptians is a subclinical infection, although progression to fulminant hepatic failure has been recorded. With the improvement in serological and molecular approaches and increasing research on HEV, it is becoming clear that HEV represents a threat for Egyptians and preventive measures should be considered to reduce the infection rate and possible complications.

After the recent Middle East Respiratory Syndrome coronavirus (MERS-CoV) pandemic in 2013, more attention has been paid to the camel as an important source of zoonotic viral infections. Almost simultaneously, in 2013, new genotypes 7 and 8 of the hepatitis E virus (HEV) were discovered in dromedary and Bactrian camels, respectively. HEV 7 was further shown to be associated with chronic viral hepatitis in a transplant recipient. In this study, serological screening for antibodies to MERS-CoV and hepatitis E virus was carried out on large camel farms in the south and west of Kazakhstan. 6.42% of the tested camels were found to be positive for antibodies to the hepatitis E virus, which indicates its circulation in local camel population. For the first time, antibodies to the hepatitis E virus were found in Bactrians, which have been little studied to date. Antibodies to MERS-CoV were not found in the camel sera.

Hepatitis E virus (HEV) infection occurs worldwide. The HEV genome includes three to four open reading frames (ORF1-4). ORF1 proteins are essential for viral replication, while the ORF3 protein is an ion channel involved in the exit of HEV from the infected cells. ORF2 proteins form the viral capsid required for HEV invasion and assembly. They also suppress interferon production and inhibit antibody-mediated neutralisation of HEV, allowing the virus to hijack the host immune response. ORF2 is the only detectable viral protein in the human liver during HEV infection and it is secreted in the plasma, stool, and urine of HEV-infected patients, making it a reliable diagnostic marker. The plasma HEV ORF2 antigen level can predict the outcome of HEV infections. Hence, monitoring HEV ORF2 antigen levels may be useful in assessing the efficacy of anti-HEV therapy. The ORF2 antigen is immunogenic and includes epitopes that can induce neutralising antibodies; therefore, it is a potential HEV vaccine candidate. In this review, we highlighted the different forms of HEV ORF2 protein and their roles in HEV pathogenesis, diagnosis, monitoring the therapeutic efficacy, and vaccine development.

The intimate relationship between virus and host cell can result in highly adapted viruses that are restricted to a single host. However, some viruses have the ability to infect multiple host species. Remarkably, hepatitis E viruses (HEV) comprise genotypes that are either 'single-host' or 'multi-host' genotypes, a trait that raises fundamental questions: Why do different genotypes differ in their host range, despite a high degree of genomic similarity? What are the underlying molecular determinants that shape species barriers? Here, we review the current knowledge of viral and host determinants that may affect the evolutionary trajectories of HEV. We also provide a perspective on techniques and methods that address open questions of HEV host range and adaptation.