Research

11 pages, 284 KiB

Open AccessArticle

Hepatitis E Virus (HEV) in Makkah, Saudi Arabia: A Population-Based Seroprevalence Study

by Mai M. El-Daly, Rajaa Al-Raddadi, Amany Alharbi, Abdulrahman E. Azhar, Amjed M. Khallaf, Ahmed M. Hassan, Osama M. Alwafi, Omaima I. Shabouni, Thamir A. Alandijany, Tian-Cheng Li, Sherif A. El-Kafrawy, Alimuddin Zumla and Esam I. Azhar

Viruses 2023, 15(2), 484; https://doi.org/10.3390/v15020484 - 09 Feb 2023

Viewed by 2309

Abstract

Background: 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. Methods: A community-based cross-sectional HEV seroprevalence study was conducted in Makkah, Saudi Arabia. Anti-HEV [...] Read more.

Background: 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. Methods: 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. Results: 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. Conclusions: 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. Full article

(This article belongs to the Special Issue Hepatitis E Virus (HEV))

13 pages, 1482 KiB

Open AccessArticle

Detection of Hepatitis E Virus Genotype 3 in Feces of Capybaras (Hydrochoeris hydrochaeris) in Brazil

by Lia Cunha, Adriana Luchs, Lais S. Azevedo, Vanessa C. M. Silva, Marcilio F. Lemos, Antonio C. Costa, Adriana P. Compri, Yasmin França, Ellen Viana, Fernanda Malta, Roberta S. Medeiros, Raquel Guiducci, Simone G. Morillo, Michele S. Gomes-Gouvea, Deyvid Amgarten, João R. R. Pinho and Regina C. Moreira

Viruses 2023, 15(2), 335; https://doi.org/10.3390/v15020335 - 24 Jan 2023

Cited by 5 | Viewed by 2744

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue Hepatitis E Virus (HEV))

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22 pages, 4756 KiB

Open AccessArticle

Geographic and Temporal Variability of Hepatitis E Virus Circulation in the Russian Federation

by Mikhail I. Mikhailov, Anastasia A. Karlsen, Ilya A. Potemkin, Olga V. Isaeva, Vera S. Kichatova, Elena Yu. Malinnikova, Fedor A. Asadi Mobarkhan, Eugeniy V. Mullin, Maria A. Lopatukhina, Victor A. Manuylov, Elena P. Mazunina, Evgeniia N. Bykonia, Denis A. Kleymenov, Liubov I. Popova, Vladimir A. Gushchin, Artem P. Tkachuk, Andrey D. Polyakov, Ahmed Mohammed Eladly, Sergey A. Solonin, Ilya V. Gordeychuk and Karen K. Kyuregyan Show full author list Hide full author list

Viruses 2023, 15(1), 37; https://doi.org/10.3390/v15010037 - 22 Dec 2022

Cited by 6 | Viewed by 2205

Abstract

The factors influencing hepatitis E virus (HEV) circulation remain largely unexplored. We investigated HEV seroprevalence in humans and the prevalence of infection in farm pigs and rabbits in different regions of the Russian Federation, as well as the genetic diversity and population dynamics [...] Read more.

The factors influencing hepatitis E virus (HEV) circulation remain largely unexplored. We investigated HEV seroprevalence in humans and the prevalence of infection in farm pigs and rabbits in different regions of the Russian Federation, as well as the genetic diversity and population dynamics of the HEV. The anti-HEV IgG antibody detection rates in the general population increase significantly with age, from 1.5% in children and adolescents under 20 years old to 4.8% in adults aged between 20 and 59 years old to 16.7% in people aged 60 years and older. HEV seroprevalence varies between regions, with the highest rate observed in Belgorod Region (16.4% compared with the national average of 4.6%), which also has the country’s highest pig population. When compared with the archival data, both increases and declines in HEV seroprevalence have been observed within the last 10 years, depending on the study region. Virus shedding has been detected in 19 out of the 21 pig farms surveyed. On one farm, the circulation of the same viral strain for five years was documented. All the human and animal strains belonged to the HEV-3 genotype, with its clade 2 sequences being predominant in pigs. The sequences are from patients, pigs, and sewage from pig farms clustered together, suggesting a zoonotic infection in humans and possible environmental contamination. The HEV-3 population size that was predicted using SkyGrid reconstruction demonstrated exponential growth in the 1970s–1990s, with a subsequent decline followed by a short rise around the year 2010, the pattern being similar to the dynamics of the pig population in the country. The HEV-3 reproduction number (Re) that was predicted using birth–death skyline analysis has fluctuated around 1 over the past 20 years in Russia but is 10 times higher in Belgorod Region. In conclusion, the HEV-3 circulation varies both geographically and temporally, even within a single country. The possible factors contributing to this variability are largely related to the circulation of the virus among farm pigs. Full article

(This article belongs to the Special Issue Hepatitis E Virus (HEV))

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13 pages, 3408 KiB

Open AccessEditor’s ChoiceArticle

A Secreted Form of the Hepatitis E Virus ORF2 Protein: Design Strategy, Antigenicity and Immunogenicity

by Zihao Chen, Shaoqi Guo, Guanghui Li, Dong Ying, Guiping Wen, Mujin Fang, Yingbin Wang, Zimin Tang, Zizheng Zheng and Ningshao Xia

Viruses 2022, 14(10), 2122; https://doi.org/10.3390/v14102122 - 26 Sep 2022

Cited by 3 | Viewed by 2155

Abstract

Hepatitis E virus (HEV) is an important public health burden worldwide, causing approximately 20 million infections and 70,000 deaths annually. The viral capsid protein is encoded by open reading frame 2 (ORF2) of the HEV genome. Most ORF2 protein present in body fluids [...] Read more.

Hepatitis E virus (HEV) is an important public health burden worldwide, causing approximately 20 million infections and 70,000 deaths annually. The viral capsid protein is encoded by open reading frame 2 (ORF2) of the HEV genome. Most ORF2 protein present in body fluids is the glycosylated secreted form of the protein (ORF2^S). A recent study suggested that ORF2^S is not necessary for the HEV life cycle. A previously reported efficient HEV cell culture system can be used to understand the origin and life cycle of ORF2^S but is not sufficient for functional research. A more rapid and productive method for yielding ORF2^S could help to study its antigenicity and immunogenicity. In this study, the ORF2^S (tPA) expression construct was designed as a candidate tool. A set of representative anti-HEV monoclonal antibodies was further used to map the functional antigenic sites in the candidates. ORF2^S (tPA) was used to study antigenicity and immunogenicity. Indirect ELISA revealed that ORF2^S (tPA) was not antigenically identical to HEV 239 antigen (p239). The ORF2^S-specific antibodies were successfully induced in one-dose-vaccinated BALB/c mice. The ORF2^S-specific antibody response was detected in plasma from HEV-infected patients. Recombinant ORF2^S (tPA) can act as a decoy to against B cells. Altogether, our study presents a design strategy for ORF2^S expression and indicates that ORF2^S (tPA) can be used for functional and structural studies of the HEV life cycle. Full article

(This article belongs to the Special Issue Hepatitis E Virus (HEV))

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17 pages, 3965 KiB

Open AccessArticle

Inhibition of Hepatitis E Virus Replication by Novel Inhibitor Targeting Methyltransferase

by Preeti Hooda, Meenakshi Chaudhary, Mohammad K. Parvez, Neha Sinha and Deepak Sehgal

Viruses 2022, 14(8), 1778; https://doi.org/10.3390/v14081778 - 15 Aug 2022

Cited by 3 | Viewed by 2219

Abstract

Hepatitis E Virus (HEV) is a quasi-enveloped virus having a single-stranded, positive-sense RNA genome (~7.2 kb), flanked with a 5′ methylated cap and a 3′ polyadenylated tail. The HEV open reading frame 1 (ORF1) encodes a 186-kDa polyprotein speculated to get processed and [...] Read more.

Hepatitis E Virus (HEV) is a quasi-enveloped virus having a single-stranded, positive-sense RNA genome (~7.2 kb), flanked with a 5′ methylated cap and a 3′ polyadenylated tail. The HEV open reading frame 1 (ORF1) encodes a 186-kDa polyprotein speculated to get processed and produce Methyltransferase (MTase), one of the four essential replication enzymes. In this study, we report the identification of the MTase inhibitor, which may potentially deplete its enzymatic activity, thus causing the cessation of viral replication. Using in silico screening through docking, we identified ten putative compounds, which were tested for their anti-MTase activity. This resulted in the identification of 3-(4-Hydroxyphenyl)propionic acid (HPPA), with an IC₅₀ value of 0.932 ± 0.15 μM, which could be perceived as an effective HEV inhibitor. Furthermore, the compound was tested for inhibition of HEV replication in the HEV culture system. The viral RNA copies were markedly decreased from ~3.2 × 10⁶ in untreated cells to ~4.3 × 10^2.8 copies in 800 μM HPPA treated cells. Therefore, we propose HPPA as a potential drug-like inhibitor against HEV-MTase, which would need further validation through in vivo analysis using animal models and the administration of Pharmacokinetic and Pharmacodynamic (PK/PD) studies. Full article

(This article belongs to the Special Issue Hepatitis E Virus (HEV))

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12 pages, 1040 KiB

Open AccessArticle

Hepatitis E Virus Seroprevalence and Associated Risk Factors in Pregnant Women Attending Antenatal Consultations in Senegal

by Abou Abdallah Malick Diouara, Seynabou Lo, Cheikh Momar Nguer, Assane Senghor, Halimatou Diop Ndiaye, Noël Magloire Manga, Fodé Danfakha, Sidy Diallo, Marie Edouard Faye Dieme, Ousmane Thiam, Babacar Biaye, Ndèye Marie Pascaline Manga, Fatou Thiam, Habibou Sarr, Gora Lo, Momar Ndour, Sébastien Paterne Manga, Nouhou Diaby, Modou Dieng, Idy Diop, Yakhya Dieye, Coumba Toure Kane, Martine Peeters and Ahidjo Ayouba Show full author list Hide full author list

Viruses 2022, 14(8), 1742; https://doi.org/10.3390/v14081742 - 09 Aug 2022

Cited by 1 | Viewed by 2125

Abstract

In West Africa, research on the hepatitis E virus (HEV) is barely covered, despite the recorded outbreaks. The low level of access to safe water and adequate sanitation is still one of the main factors of HEV spread in developing countries. HEV infection [...] Read more.

In West Africa, research on the hepatitis E virus (HEV) is barely covered, despite the recorded outbreaks. The low level of access to safe water and adequate sanitation is still one of the main factors of HEV spread in developing countries. HEV infection induces acute or sub-clinical liver diseases with a mortality rate ranging from 0.5 to 4%. The mortality rate is more alarming (15 to 25%) among pregnant women, especially in the last trimester of pregnancy. Herein, we conducted a multicentric socio-demographic and seroepidemiological survey of HEV in Senegal among pregnant women. A consecutive and non-redundant recruitment of participants was carried out over the period of 5 months, from March to July 2021. A total of 1227 consenting participants attending antenatal clinics responded to a standard questionnaire. Plasma samples were collected and tested for anti-HEV IgM and IgG by using the WANTAI HEV-IgM and IgG ELISA assay. The overall HEV seroprevalence was 7.8% (n = 96), with 0.5% (n = 6) and 7.4% (n = 91) for HEV IgM and HEV IgG, respectively. One of the participant samples was IgM/IgG-positive, while four were declared indeterminate to anti-HEV IgM as per the manufacturer’s instructions. From one locality to another, the seroprevalence of HEV antibodies varied from 0 to 1% for HEV IgM and from 1.5 to 10.5% for HEV IgG. The data also showed that seroprevalence varied significantly by marital status (p < 0.0001), by the regularity of income (p = 0.0043), and by access to sanitation services (p = 0.0006). These data could serve as a basis to setup national prevention strategies focused on socio-cultural, environmental, and behavioral aspects for a better management of HEV infection in Senegal. Full article

(This article belongs to the Special Issue Hepatitis E Virus (HEV))

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12 pages, 2401 KiB

Open AccessArticle

Independent Evaluation of Cell Culture Systems for Hepatitis E Virus

by Nicholas Chew, Jianwen Situ, Shusheng Wu, Weiming Yao and Siddharth Sridhar

Viruses 2022, 14(6), 1254; https://doi.org/10.3390/v14061254 - 09 Jun 2022

Cited by 8 | Viewed by 2202

Abstract

Hepatitis E virus (HEV) infection in humans is primarily caused by genotypes within Paslahepevirus species balayani (HEV-A). Rocahepevirus species ratti (HEV-C1, otherwise known as rat HEV) can also infect humans. HEV grows poorly in cell culture. Recent studies have reported that hyper-confluent cell [...] Read more.

Hepatitis E virus (HEV) infection in humans is primarily caused by genotypes within Paslahepevirus species balayani (HEV-A). Rocahepevirus species ratti (HEV-C1, otherwise known as rat HEV) can also infect humans. HEV grows poorly in cell culture. Recent studies have reported that hyper-confluent cell layers, amphotericin B, MgCl₂, progesterone, and dimethyl sulfoxide (DMSO) increase HEV yield in vitro. Here, we describe an independent evaluation of the effectiveness of these modifications in improving the yield of HEV-A genotype 4 (HEV-A4) and HEV-C1 from clinical samples in PLC/PRF/5 cells. We found that amphotericin B, MgCl₂, and DMSO increased HEV yield from high-viral-load patient stool samples, while progesterone was not effective. Yield of HEV-C1 was lower than HEV-A4 across all medium conditions, but was boosted by DMSO. HEV-A4 could be maintained for over 18 months in amphotericin B- and MgCl₂-containing medium, with the demonstration of viral antigen in supernatants and infected cells. We also evaluated various protocols to remove pseudo-envelopes from cell culture-derived HEV. Treating cell culture supernatant with NP-40 was the most effective. Our findings identify key modifications that boost HEV growth in vitro and illustrate the importance of independent verification of such studies using diverse HEV variants and cell lines. Full article

(This article belongs to the Special Issue Hepatitis E Virus (HEV))

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7 pages, 851 KiB

Open AccessCommunication

Diagnostic Performance of an Automated System for Assaying Anti-Hepatitis E Virus Immunoglobulins M and G Compared with a Conventional Microplate Assay

by Florence Abravanel, Delphine Parraud, Sabine Chapuy-Regaud, Marcel Miedouge, Estelle Bonnin, Margaux Larrieu, Alexandre Aversenq, Sébastien Lhomme and Jacques Izopet

Viruses 2022, 14(5), 1065; https://doi.org/10.3390/v14051065 - 17 May 2022

Cited by 7 | Viewed by 1979

Abstract

To evaluate the diagnostic performance of the Liaison^® Murex anti-HEV IgM and IgG assays running on the Liaison^® instrument and compare the results with those obtained with Wantai HEV assays. We tested samples collected in immunocompetent and immunocompromised patients during the [...] Read more.

To evaluate the diagnostic performance of the Liaison^® Murex anti-HEV IgM and IgG assays running on the Liaison^® instrument and compare the results with those obtained with Wantai HEV assays. We tested samples collected in immunocompetent and immunocompromised patients during the acute (HEV RNA positive, anti-HEV IgM positive) and the post-viremic phase (HEV RNA negative, anti-HEV IgM positive) of infections. The specificity was assessed by testing HEV RNA negative/anti-HEV IgG-IgM negative samples. The clinical sensitivity of the Liaison^® IgM assay was 100% for acute-phase samples (56/56) and 57.4% (27/47) for post-viremic samples from immunocompetent patients. It was 93.8% (30/32) for acute-phase (viremic) samples and 71%% (22/31) for post-viremic samples from immunocompromised patients. The clinical sensitivity of the Liaison^® IgG assay was 100% for viremic samples (56/56) and 94.6% (43/47) for post-viremic samples from immunocompetent patients. It was 84.3% (27/32) for viremic samples and 93.5% (29/31) for post-viremic samples from immunocompromised patients. Specificity was very high (>99%) in both populations. We checked the limit of detection stated for the Liaison^® IgG assay (0.3 U/mL). The clinical performance of the Liaison^® ANTI-HEV assays was good. These rapid, automated assays for detecting anti-HEV antibodies will greatly enhance the arsenal for diagnosing HEV infections. Full article

(This article belongs to the Special Issue Hepatitis E Virus (HEV))

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Review

Jump to: Research, Other

19 pages, 385 KiB

Open AccessReview

Hepatitis E Virus Research in Brazil: Looking Back and Forwards

by Jaqueline Mendes de Oliveira, Debora Regina Lopes dos Santos and Marcelo Alves Pinto

Viruses 2023, 15(2), 548; https://doi.org/10.3390/v15020548 - 16 Feb 2023

Cited by 4 | Viewed by 1624

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue Hepatitis E Virus (HEV))

15 pages, 2208 KiB

Open AccessReview

Hepatitis E Virus (HEV) Synopsis: General Aspects and Focus on Bangladesh

by Asma Binte Aziz, Joakim Øverbø, Susanne Dudman, Cathinka Halle Julin, Yoon Jeong Gabby Kwon, Yasmin Jahan, Mohammad Ali and Jennifer L. Dembinski

Viruses 2023, 15(1), 63; https://doi.org/10.3390/v15010063 - 24 Dec 2022

Cited by 3 | Viewed by 2487

Abstract

HEV is the most common cause of acute hepatitis globally. This review summarizes the latest knowledge on the epidemiology, clinical characteristics, testing, and treatment of HEV infection. We also focused on Bangladesh to highlight the distinct challenges and the possible remedies. In low-income [...] Read more.

HEV is the most common cause of acute hepatitis globally. This review summarizes the latest knowledge on the epidemiology, clinical characteristics, testing, and treatment of HEV infection. We also focused on Bangladesh to highlight the distinct challenges and the possible remedies. In low-income settings, the virus is mainly transmitted between people by fecal contamination of drinking water causing large outbreaks, and sporadic cases. The disease is usually mild and self-limiting acute hepatitis. Still, pregnant women and their offspring in low-income countries are at particular risk for severe disease, with up to 20% maternal mortality. Despite the high burden of the disease, HEV remains a relatively neglected virus, with detection hampered by costly tests and a lack of suitable treatments. Molecular PCR diagnostics, together with ELISA antibody tests, remain the preferred methods for diagnosis of HEV; however, rapid bedside diagnostics are available and could offer a practical alternative, especially in low-income countries. One vaccine (HEV 239) is only available in China and Pakistan, as efficacy against the other genotypes remains uncertain. The effectiveness trial conducted in Bangladesh might lead the way in gathering more efficacy data and could, together with improved surveillance and raised awareness, dramatically reduce the global burden of HEV. Full article

(This article belongs to the Special Issue Hepatitis E Virus (HEV))

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Other

Jump to: Research, Review

8 pages, 384 KiB

Open AccessPerspective

Unmet Needs for the Treatment of Chronic Hepatitis E Virus Infection in Immunocompromised Patients

by Nassim Kamar, Arnaud Del Bello, Florence Abravanel, Qiuwei Pan and Jacques Izopet

Viruses 2022, 14(10), 2116; https://doi.org/10.3390/v14102116 - 25 Sep 2022

Cited by 4 | Viewed by 1819

Abstract

Hepatitis E virus (HEV) is the most prevalent hepatitis virus worldwide. Genotypes 3 (HEV3) and 4 (HEV4) as well as rat HEV can lead to chronic hepatitis E and cirrhosis in immunosuppressed patients. Within the last decade, several options for treating chronic hepatitis [...] Read more.

Hepatitis E virus (HEV) is the most prevalent hepatitis virus worldwide. Genotypes 3 (HEV3) and 4 (HEV4) as well as rat HEV can lead to chronic hepatitis E and cirrhosis in immunosuppressed patients. Within the last decade, several options for treating chronic hepatitis have been developed and have achieved a sustained virological response. However, there are still unmet needs such as optimizing immunosuppression to allow HEV clearance with or without ribavirin, as well as alternative therapies to ribavirin that are discussed in this paper. Full article

(This article belongs to the Special Issue Hepatitis E Virus (HEV))

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