Dataset Information

Chronic equine hepacivirus infection in an adult gelding with severe hepatopathy.

ABSTRACT: BACKGROUND:Equine hepacivirus (EqHV) in equids represents the closest homologue to hepatitis C virus (HCV) infecting humans. A majority of HCV infected patients develop a chronic course of infection leading to liver fibrosis, cirrhosis and liver failure. However, in horses mostly transient mild subclinical infections are reported for EqHV to date. OBJECTIVES:EqHV can be involved in chronic liver diseases of horses. METHODS:Biochemical parameters in serum samples were measured. Viral load was determined using qPCR. Next generation sequencing (NGS) of serum was performed. Liver tissue was stained with haematoxylin and eosin and analysed for viral RNA with fluorescent in situ-hybridization. RESULTS:The horse showed symptoms of severe hepatopathy and was chronically infected with EqHV. Viral RNA was detectable in the liver during disease. To rule out other infectious agents NGS was performed and showed the highest abundance for EqHV. The identified virus sequence was similar to other circulating equine hepaciviruses. CONCLUSIONS:EqHV can be associated with liver disease in horses. Whether it causes the disease or contributes in a multifactorial manner needs further investigation.

SUBMITTER: Tegtmeyer B

PROVIDER: S-EPMC6682795 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Chronic equine hepacivirus infection in an adult gelding with severe hepatopathy.

Tegtmeyer Birthe B Echelmeyer Julia J Pfankuche Vanessa M VM Puff Christina C Todt Daniel D Fischer Nicole N Durham Andy A Feige Karsten K Baumgärtner Wolfgang W Steinmann Eike E Cavalleri Jessika-M V JV

Veterinary medicine and science 20190703 3

<h4>Background</h4>Equine hepacivirus (EqHV) in equids represents the closest homologue to hepatitis C virus (HCV) infecting humans. A majority of HCV infected patients develop a chronic course of infection leading to liver fibrosis, cirrhosis and liver failure. However, in horses mostly transient mild subclinical infections are reported for EqHV to date.<h4>Objectives</h4>EqHV can be involved in chronic liver diseases of horses.<h4>Methods</h4>Biochemical parameters in serum samples were measur ...[more]

PMID: 31267690

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Project description:UnlabelledEquine hepacivirus (EHcV) has been identified as a closely related homologue of hepatitis C virus (HCV) in the United States, the United Kingdom, and Germany, but not in Asian countries. In this study, we genetically and serologically screened 31 serum samples obtained from Japanese-born domestic horses for EHcV infection and subsequently identified 11 PCR-positive and 7 seropositive serum samples. We determined the full sequence of the EHcV genome, including the 3' untranslated region (UTR), which had previously not been completely revealed. The polyprotein of a Japanese EHcV strain showed approximately 95% homology to those of the reported strains. HCV-like cis-acting RNA elements, including the stem-loop structures of the 3' UTR and kissing-loop interaction were deduced from regions around both UTRs of the EHcV genome. A comparison of the EHcV and HCV core proteins revealed that Ile(190) and Phe(191) of the EHcV core protein could be important for cleavage of the core protein by signal peptide peptidase (SPP) and were replaced with Ala and Leu, respectively, which inhibited intramembrane cleavage of the EHcV core protein. The loss-of-function mutant of SPP abrogated intramembrane cleavage of the EHcV core protein and bound EHcV core protein, suggesting that the EHcV core protein may be cleaved by SPP to become a mature form. The wild-type EHcV core protein, but not the SPP-resistant mutant, was localized on lipid droplets and partially on the lipid raft-like membrane in a manner similar to that of the HCV core protein. These results suggest that EHcV may conserve the genetic and biological properties of HCV.ImportanceEHcV, which shows the highest amino acid or nucleotide homology to HCV among hepaciviruses, was previously reported to infect horses from Western, but not Asian, countries. We herein report EHcV infection in Japanese-born horses. In this study, HCV-like RNA secondary structures around both UTRs were predicted by determining the whole-genome sequence of EHcV. Our results also suggest that the EHcV core protein is cleaved by SPP to become a mature form and then is localized on lipid droplets and partially on lipid raft-like membranes in a manner similar to that of the HCV core protein. Hence, EHcV was identified as a closely related homologue of HCV based on its genetic structure as well as its biological properties. A clearer understanding of the epidemiology, genetic structure, and infection mechanism of EHcV will assist in elucidating the evolution of hepaciviruses as well as the development of surrogate models for the study of HCV.

Project description:Reports of newly discovered equine hepatotropic flavi- and parvoviruses have emerged throughout the last decade in many countries, the discovery of which has stimulated a great deal of interest and clinical research. Although commonly detected in horses without signs of disease, equine parvovirus hepatitis (EqPV-H) and equine hepacivirus (EqHV) have been associated with liver disease, including following the administration of contaminated anti-toxin. Our aim was to determine whether EqPV-H and EqHV are present in Australian horses and whether EqPV-H was present in French horses and to examine sequence diversity between strains of both viruses amongst infected horses on either side of the globe. Sera from 188 Australian horses and 256 French horses from horses with and without clinical signs of disease were collected. Twelve out of 256 (4.7%) and 6 out of 188 (3.2%) French and Australian horses, respectively, were positive for the molecular detection of EqPV-H. Five out of 256 (1.9%) and 21 out of 188 (11.2%) French and Australian horses, respectively, were positive for the molecular detection of EqHV. Australian strains for both viruses were genomically clustered, in contrast to strains from French horses, which were more broadly distributed. The findings of this preliminary survey, with the molecular detection of EqHV and EqPV-H in Australia and the latter in France, adds to the growing body of awareness regarding these recently discovered hepatotropic viruses. It has provided valuable information not just in terms of geographic endemicity but will guide equine clinicians, carers, and authorities regarding infectious agents and potential impacts of allogenic tissue contamination. Although we have filled many gaps in the world map regarding equine hepatotropic viruses, further prospective studies in this emerging field may be useful in terms of elucidating risk factors and pathogenesis of these pathogens and management of cases in terms of prevention and diagnosis.

Dataset Information

Chronic equine hepacivirus infection in an adult gelding with severe hepatopathy.

Publications

Chronic equine hepacivirus infection in an adult gelding with severe hepatopathy.

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