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9 pages, 253 KiB

Open AccessArticle

Hepatitis E, Schistosomiasis and Echinococcosis–Prevalence in a Cohort of Pregnant Migrants in Germany and Their Influence on Fetal Growth Restriction

by Janine Zöllkau, Juliane Ankert, Mathias W. Pletz, Sasmita Mishra, Gregor Seliger, Silvia M. Lobmaier, Clarissa U. Prazeres Da Costa, Vera Seidel, Katharina von Weizsäcker, Alexandra Jablonka, Christian Dopfer, Michael Baier, Thomas Horvatits, Ingrid Reiter-Owona, Tanja Groten and Benjamin T. Schleenvoigt

Pathogens 2022, 11(1), 58; https://doi.org/10.3390/pathogens11010058 - 3 Jan 2022

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Abstract

Background: Infections, as well as adverse birth outcomes, may be more frequent in migrant women. Schistosomiasis, echinococcosis, and hepatitis E virus (HEV) seropositivity are associated with the adverse pregnancy outcomes of fetal growth restriction and premature delivery. Methods: A cohort study of 82 [...] Read more.

Background: Infections, as well as adverse birth outcomes, may be more frequent in migrant women. Schistosomiasis, echinococcosis, and hepatitis E virus (HEV) seropositivity are associated with the adverse pregnancy outcomes of fetal growth restriction and premature delivery. Methods: A cohort study of 82 pregnant women with a history of migration and corresponding delivery of newborns in Germany was conducted. Results: Overall, 9% of sera tested positive for anti-HEV IgG. None of the patients tested positive for anti-HEV IgM, schistosomiasis, or echinococcus serology. Birth weights were below the 10th percentile for gestational age in 8.5% of the neonates. No association between HEV serology and fetal growth restriction (FGR) frequency was found. Conclusions: In comparison to German baseline data, no increased risk for HEV exposure or serological signs of exposure against schistosomiasis or echinococcosis could be observed in pregnant migrants. An influence of the anti-HEV serology status on fetal growth restriction could not be found. Full article

(This article belongs to the Special Issue Hepatitis E and the One-Health Aspect: A Threat to Mankind and Animality?)

18 pages, 3819 KiB

Open AccessArticle

The Capsid (ORF2) Protein of Hepatitis E Virus in Feces Is C-Terminally Truncated

by Takashi Nishiyama, Koji Umezawa, Kentaro Yamada, Masaharu Takahashi, Satoshi Kunita, Mulyanto, Isao Kii and Hiroaki Okamoto

Pathogens 2022, 11(1), 24; https://doi.org/10.3390/pathogens11010024 - 26 Dec 2021

Cited by 9 | Viewed by 3148

Abstract

The hepatitis E virus (HEV) is a causative agent of hepatitis E. HEV virions in circulating blood and culture media are quasi-enveloped, while those in feces are nonenveloped. The capsid (ORF2) protein associated with an enveloped HEV virion is reported to comprise the [...] Read more.

The hepatitis E virus (HEV) is a causative agent of hepatitis E. HEV virions in circulating blood and culture media are quasi-enveloped, while those in feces are nonenveloped. The capsid (ORF2) protein associated with an enveloped HEV virion is reported to comprise the translation product of leucine 14/methionine 16 to 660 (C-terminal end). However, the nature of the ORF2 protein associated with fecal HEV remains unclear. In the present study, we compared the molecular size of the ORF2 protein among fecal HEV, cell-culture-generated HEV (HEVcc), and detergent-treated protease-digested HEVcc. The ORF2 proteins associated with fecal HEV were C-terminally truncated and showed the same size as those of the detergent-treated protease-digested HEVcc virions (60 kDa), in contrast to those of the HEVcc (68 kDa). The structure prediction of the ORF2 protein (in line with previous studies) demonstrated that the C-terminal region (54 amino acids) of an ORF2 protein is in flux, suggesting that proteases target this region. The nonenveloped nondigested HEV structure prediction indicates that the C-terminal region of the ORF2 protein moves to the surface of the virion and is unnecessary for HEV infection. Our findings clarify the maturation of nonenveloped HEV and will be useful for studies on the HEV lifecycle. Full article

(This article belongs to the Special Issue Hepatitis E and the One-Health Aspect: A Threat to Mankind and Animality?)

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6 pages, 451 KiB

Open AccessArticle

Lack of Evidence for an Association between Previous HEV Genotype-3 Exposure and Glomerulonephritis in General

by Sven Pischke, Sarah Tamanaei, Maria Mader, Julian Schulze zur Wiesch, Christine Petersen-Benz, Munif Haddad, Marylyn M. Addo, Tilman Schmidt, Tobias B. Huber, Christian F. Krebs, Oliver M. Steinmetz, Jan E. Turner, Elion Hoxha and Thomas Horvatits

Pathogens 2022, 11(1), 18; https://doi.org/10.3390/pathogens11010018 - 23 Dec 2021

Cited by 4 | Viewed by 2528

Abstract

Among numerous other immune-mediated diseases, glomerulonephritis has also been suspected to be an extrahepatic manifestation of HEV infection. In this prospective study, we tested 108 patients with glomerulonephritis and 108 age- and sex-matched healthy controls at the University Hospital Hamburg Eppendorf, Hamburg, Germany, [...] Read more.

Among numerous other immune-mediated diseases, glomerulonephritis has also been suspected to be an extrahepatic manifestation of HEV infection. In this prospective study, we tested 108 patients with glomerulonephritis and 108 age- and sex-matched healthy controls at the University Hospital Hamburg Eppendorf, Hamburg, Germany, for anti-HEV IgG (Wantai test) as a marker for previous HEV exposure. A total of 24 patients (22%) tested positive for anti-HEV IgG. Males tended to be more frequently anti-HEV IgG positive (29%) in comparison to females (16%). However, this does not reach statistical significance (p = 0.07). Anti-HEV IgG positive patients were older in comparison to negative patients (mean 53 vs. 45 years, p = 0.05). The kidney function seems to be slightly decreased in anti-HEV IgG positive patients in comparison to and anti-HEV IgG negative patients basing on creatinine (p = 0.04) and glomerular filtration rate (GFR) (p = 0.05). Slightly higher values of bilirubin could be found in IgG positive patients (p = 0.04). Anti-HEV-IgG seropositivity rate (22%) in glomerulonephritis patients, did not differ significantly in comparison to an age- and sex-matched control cohort of healthy blood donors (31/108 positive, 29%). A total of 2/2 patients with membranoproliferative glomerulonephritis (MPGN) tested anti-HEV IgG positive (p = 0.002 in comparison to glomerulonephritis patients with other subtypes). In conclusion, our findings indicate that previous HEV exposure in a region where GT3 is endemic is not associated with glomerulonephritis in general. However, the subgroup of MPGN patients should be investigated in future studies. Furthermore, future studies are needed to investigate whether the observed association between anti-HEV IgG positivity and reduced GFR in glomerulonephritis patients is HEV associated or is an age-related effect. Full article

(This article belongs to the Special Issue Hepatitis E and the One-Health Aspect: A Threat to Mankind and Animality?)

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13 pages, 12159 KiB

Open AccessFeature PaperArticle

Distribution and Genetic Diversity of Hepatitis E Virus in Wild and Domestic Rabbits in Australia

by Maria Jenckel, Ina Smith, Tegan King, Peter West, Patrick L. Taggart, Tanja Strive and Robyn N. Hall

Pathogens 2021, 10(12), 1637; https://doi.org/10.3390/pathogens10121637 - 17 Dec 2021

Cited by 6 | Viewed by 3649

Abstract

In 2020, Hepatitis E virus (HEV) was detected for the first time in Australian rabbits. To improve our understanding of the genetic diversity and distribution of the virus, 1635 rabbit liver samples from locations across Australia were screened via RT-qPCR for HEV. HEV [...] Read more.

In 2020, Hepatitis E virus (HEV) was detected for the first time in Australian rabbits. To improve our understanding of the genetic diversity and distribution of the virus, 1635 rabbit liver samples from locations across Australia were screened via RT-qPCR for HEV. HEV genomes were amplified and sequenced from 48 positive samples. Furthermore, we tested 380 serum samples from 11 locations across Australia for antibodies against HEV. HEV was detected in rabbits from all states and territories, except the Northern Territory. Seroprevalence varied between locations (from 0% to 22%), demonstrating that HEV is widely distributed in rabbit populations across Australia. Phylogenetic analyses showed that Australian HEV sequences are genetically diverse and that HEV was likely introduced into Australia independently on several occasions. In summary, this study broadens our understanding of the genetic diversity of rabbit HEV globally and shows that the virus is endemic in both domestic and wild rabbit populations in Australia. Full article

(This article belongs to the Special Issue Hepatitis E and the One-Health Aspect: A Threat to Mankind and Animality?)

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12 pages, 1550 KiB

Open AccessArticle

Serological Evidence of Hepatitis E Virus Infection in Semi-Domesticated Eurasian Tundra Reindeer (Rangifer tarandus tarandus) in Norway

by Christine Hanssen Rinaldo, Ingebjørg Helena Nymo, Javier Sánchez Romano, Eva Marie Breines, Francisco Javier Ancin Murguzur and Morten Tryland

Pathogens 2021, 10(12), 1542; https://doi.org/10.3390/pathogens10121542 - 25 Nov 2021

Cited by 6 | Viewed by 2800

Abstract

Hepatitis E virus (HEV) is a common cause of viral hepatitis in humans. In developing countries, HEV-infections seem to be mainly associated with pigs, but other animal species may be involved in viral transmission. Recently, anti-HEV antibodies were detected in Norwegian wild reindeer. [...] Read more.

Hepatitis E virus (HEV) is a common cause of viral hepatitis in humans. In developing countries, HEV-infections seem to be mainly associated with pigs, but other animal species may be involved in viral transmission. Recently, anti-HEV antibodies were detected in Norwegian wild reindeer. Here, we investigated anti-HEV seroprevalence in Norwegian semi-domesticated reindeer, animals in closer contact with humans than their wild counterparts. Blood samples (n = 516) were obtained from eight reindeer herds during the period 2013–2017 and analysed with a commercial enzyme-linked immunosorbent assay designed for detecting anti-HEV antibodies in livestock. Antibodies were found in all herds and for all sampling seasons. The overall seroprevalence was 15.7% (81/516), with adults showing a slightly higher seroprevalence (18.0%, 46/256) than calves (13.5%, 35/260, p = 0.11). The seroprevalence was not influenced by gender or latitude, and there was no temporal trend (p > 0.15). A positive association between the presence of anti-HEV antibodies and antibodies against alphaherpesvirus and pestivirus, detected in a previous screening, was found (p < 0.05). We conclude that Norwegian semi-domesticated reindeer are exposed to HEV or an antigenically similar virus. Whether the virus is affecting reindeer health or infects humans and poses a threat for human health remains unknown and warrants further investigations. Full article

(This article belongs to the Special Issue Hepatitis E and the One-Health Aspect: A Threat to Mankind and Animality?)

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9 pages, 1430 KiB

Open AccessArticle

Prevalence of Hepatitis E Virus Infection among Laboratory Rabbits in China

by Lin Wang, Chunnan Liang, Xiaobo Li, Ji Wang, Rui Fu, Jin Xing, Jingyi Shu, Chenyan Zhao and Weijin Huang

Pathogens 2021, 10(6), 780; https://doi.org/10.3390/pathogens10060780 - 21 Jun 2021

Cited by 2 | Viewed by 2489

Abstract

Hepatitis E virus (HEV) is zoonotic and the leading cause of acute viral hepatitis worldwide. Rabbit HEV can infect humans and is prevalent globally. It is reported that laboratory rabbits are also naturally infected with HEV. Therefore, it is important to investigate in [...] Read more.

Hepatitis E virus (HEV) is zoonotic and the leading cause of acute viral hepatitis worldwide. Rabbit HEV can infect humans and is prevalent globally. It is reported that laboratory rabbits are also naturally infected with HEV. Therefore, it is important to investigate in a large scale the prevalence of HEV in laboratory rabbits. Serum samples were collected from 649 laboratory rabbits of 13 different commercial vendors in Beijing, China, from 2017 to 2019, and anti-HEV and HEV antigen (Ag) were tested. Fecal samples were collected from 50 laboratory rabbits from one of the vendors for HEV RNA detection. Six laboratory rabbits with natural HEV infection were euthanized and their liver, kidney, bile and urine samples were collected for HEV RNA quantification. Liver tissues were subjected to histopathology analysis. The overall positive rates of anti-HEV antibodies and HEV-Ag are 2.6% (15/588) and 7.9% (51/649), respectively. HEV RNA was detected in 12.0% (6/50) of the rabbits. High viral load of HEV RNA was detected in liver and bile samples. Liver inflammation was observed. HEV is circulating in laboratory rabbit population in China. Strict screening is crucial to ensure experimental accuracy and prevent zoonotic transmission to research personnel. Full article

(This article belongs to the Special Issue Hepatitis E and the One-Health Aspect: A Threat to Mankind and Animality?)

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11 pages, 355 KiB

Open AccessArticle

HEV-Associated Neuralgic Amyotrophy: A Multicentric Case Series

by Johannes H. Bannasch, Benjamin Berger, Claus-Peter Schwartkop, Marco Berning, Oliver Goetze, Marcus Panning, Miriam Fritz-Weltin, George Trendelenburg, Mathias Gelderblom, Marc Lütgehetmann, Fridrike Stute, Thomas Horvatits, Meike Dirks, Christoph Antoni, Patrick Behrendt and Sven Pischke

Pathogens 2021, 10(6), 672; https://doi.org/10.3390/pathogens10060672 - 30 May 2021

Cited by 2 | Viewed by 3038

Abstract

Background: Neuralgic amyotrophy (NA) has been described as a possible extrahepatic manifestation of hepatitis E virus (HEV) infection. Usually, HEV-associated NA occurs bilaterally. The clinical characteristics determining the course of HEV-associated NA have still not been defined. Methods: In this retrospective multicentric case [...] Read more.

Background: Neuralgic amyotrophy (NA) has been described as a possible extrahepatic manifestation of hepatitis E virus (HEV) infection. Usually, HEV-associated NA occurs bilaterally. The clinical characteristics determining the course of HEV-associated NA have still not been defined. Methods: In this retrospective multicentric case series, 16 patients with HEV-associated NA were studied and compared to 176 HEV patients without NA in terms of their age, sex, and ALT levels. Results: Neither gender distribution (75% vs. 67% male) nor age (47 vs. 48 years median) differed significantly between the NA patients and controls. Eight NA patients (50%) presented with bilateral involvement—seven of these had right-side dominance and one had left-side dominance. Thirteen cases (81%) were hospitalized. Eight of these patients stayed in hospital for five to seven days, and five patients stayed for up to two weeks. The time from the onset of NA to the HEV diagnosis, as well as the diagnostic and therapeutic proceedings, showed a large variability. In total, 13 (81%) patients received treatment: 1/13 (8%) received intravenous immunoglobulins, 8/13 (62%) received glucocorticoids, 3/13 (23%) received ribavirin, and 6/13 (46%) received pregabalin/gabapentin. Patients with ages above the median (47 years) were more likely to be treated (p = 0.001). Conclusion: HEV-associated NA causes a relevant morbidity. In our case series neither the type of treatment nor the time of initiation of therapy had a significant effect on the duration of hospitalization or the course of the disease. The clinical presentation, the common diagnostic and therapeutic procedures, and the patients’ characteristics showed large variability, demonstrating the necessity of standardized protocols for this rare but relevant disease. Full article

(This article belongs to the Special Issue Hepatitis E and the One-Health Aspect: A Threat to Mankind and Animality?)

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Review

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13 pages, 977 KiB

Open AccessReview

Cellular Organelles Involved in Hepatitis E Virus Infection

by Xing Liu, Menghang Wang and Xin Yin

Pathogens 2021, 10(9), 1206; https://doi.org/10.3390/pathogens10091206 - 17 Sep 2021

Cited by 4 | Viewed by 3483

Abstract

Hepatitis E virus (HEV), a major cause of acute hepatitis worldwide, infects approximately 20 million individuals annually. HEV can infect a wide range of mammalian and avian species, and cause frequent zoonotic spillover, increasingly raising public health concerns. To establish a successful infection, [...] Read more.

Hepatitis E virus (HEV), a major cause of acute hepatitis worldwide, infects approximately 20 million individuals annually. HEV can infect a wide range of mammalian and avian species, and cause frequent zoonotic spillover, increasingly raising public health concerns. To establish a successful infection, HEV needs to usurp host machineries to accomplish its life cycle from initial attachment to egress. However, relatively little is known about the HEV life cycle, especially the functional role(s) of cellular organelles and their associated proteins at different stages of HEV infection. Here, we summarize current knowledge regarding the relation of HEV with the different cell organelles during HEV infection. Furthermore, we discuss the underlying mechanisms by which HEV infection is precisely regulated in infected cells and the modification of host cell organelles and their associated proteins upon HEV infection. Full article

(This article belongs to the Special Issue Hepatitis E and the One-Health Aspect: A Threat to Mankind and Animality?)

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