Hepatitis C virus (HCV) has a very narrow species and tissue tropism and efficiently replicates only in humans and the chimpanzee. Recently, several studies identified close relatives to HCV in different animal species. Among these novel viruses, the nonprimate hepaciviruses (NPHV) that infect horses are the closest relatives of HCV described to date. In this study, we analyzed the NPHV prevalence in northern Germany and characterized the clinical course of infection and viral tissue tropism to explore the relevance of HCV-related horse viruses as a model for HCV infection. We found that approximately 31.4% of 433 horses were seropositive for antibodies (Abs) against NPHV and approximately 2.5% carried viral RNA. Liver function analyses revealed no indication for hepatic impairment in 7 of 11 horses. However, serum gamma-glutamyl transferase (GGT) concentrations were mildly elevated in 3 horses, and 1 horse displayed even highly elevated GGT levels. Furthermore, we observed that NPHV infection could be cleared in individual horses with a simultaneous emergence of nonstructural (NS)3-specific Abs and transient elevation of serum levels of liver-specific enzymes indicative for a hepatic inflammation. In other individual horses, chronic infections could be observed with the copresence of viral RNA and NS3-specific Abs for over 6 months. For the determination of viral tissue tropism, we analyzed different organs and tissues of 1 NPHV-positive horse using quantitative real-time polymerase chain reaction and fluorescent in situ hydridization and detected NPHV RNA mainly in the liver and at lower amounts in other organs. Conclusion: Similar to HCV infections in humans, this work demonstrates acute and chronic stages of NPHV infection in horses with viral RNA detectable predominantly within the liver. (HEPATOLOGY 2015;61:447-459) G lobally, an estimated 160 million people are chronically infected with hepatitis C virus (HCV) 1 and are therefore at a high risk for developing severe liver damage, including hepatic steatosis, fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). 2 Acute HCV infection is asymptomatic in

Equine metabolic syndrome (EMS) is a widely recognized collection of risk factors for endocrinopathic laminitis. The most important of these risk factors is insulin dysregulation (ID). Clinicians and horse owners must recognize the presence of these risk factors so that they can be targeted and controlled to reduce the risk of laminitis attacks. Diagnosis of EMS is based partly on the horse's history and clinical examination findings, and partly on laboratory testing. Several choices of test exist which examine different facets of ID and other related metabolic disturbances. EMS is controlled mainly by dietary strategies and exercise programs that aim to improve insulin regulation and decrease obesity where present. In some cases, pharmacologic aids might be useful. Management of an EMS case is a long‐term strategy requiring diligence and discipline by the horse's carer and support and guidance from their veterinarians.

ZusammenfassungGrundlage der Untersuchung waren die Krankengeschichten von 55 Pferden, die von 1996Pferden, die von -1999 The records of 55 horses with paranasal sinus disease that were admitted to the Equine clinic, University of Zurich in the years from 1996 to 1999 were reviewed. The horses were 26 mares, 28 geldings and 1 stallion of different breeds aged between 4 and 30 years (10.9 ± 5.3). Physical examination, rhinoscopy, diagnostic imaging, treatment and prognosis were evaluated. Dental disease (n=34) was the most common cause of chronic sinusitis. The typical clinical sign of sinusitis was nasal discharge in 52 cases that was unilateral in 49 cases. In 29 horses the nasal discharge was purulent and had a fetid odor resulting from dental disease in 28 cases. With radiography in 47 cases a fluid line could be visualized in 1 or more sinuses. Signs of dental involvement in 1 or more tooth roots were suspected in 39 cases. However, only in 20 cases it could be diagnosed with certainty based on the radiographs. Twentyfive horses were treated conservatively. Of these horses 5 had to undergo surgery after conservative treatment had failed. Altogether 21 horses underwent surgery. One tooth had to be removed in 13 cases and 2 teeth in one case, respectively. They were M1 (n=8), PM4 (n=5), M2 (n=1) or PM3 (n=1). Postoperative complications were common and consisted of chronic sinusitis (n=5), draining tracts (n=4), oral fistula (n=4) or facial wound dehiscence (n=2). Because of complications 6 horses required an additional surgical procedure. Twentysix horses that were treated for either primary sinusitis or sinusitis caused by dental disease were available for follow-up after 2 months. At this time 18 horses revealed no clinical signs of sinusitis.

Preclinical studies investigating new therapeutic principles against melanoma are presently being carried out in mouse models; however, these are not optimal. Here we describe a novel animal model using gray horses. These animals spontaneously develop metastatic melanoma that resembles human disease and is thus highly relevant for preclinical studies testing new immunotherapy protocols. We found that injection of plasmid DNA coding for the human cytokine interleukin 12 into established metastases induced significant regression in all 12 treated lesions in a total of 7 horses. Complete disappearance was observed in one treated lesion, with no recurrence after 6 months. No adverse events have been observed in any of the animals during and after treatment. These results demonstrate the effectiveness and safety of interleukin 12 encoding plasmid DNA therapy against established metastatic disease in a large animal model and serve as a basis for a clinical trial.

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Hepatitis C virus (HCV) displays a restricted host species tropism and only humans and chimpanzees are susceptible to infection. A robust immunocompetent animal model is still lacking, hampering mechanistic analysis of virus pathogenesis, immune control, and prophylactic vaccine development. The closest homolog of HCV is the equine nonprimate hepacivirus (NPHV), which shares similar features with HCV and thus represents an animal model to study hepacivirus infections in their natural hosts. We aimed to dissect equine immune responses after experimental NPHV infection and conducted challenge experiments to investigate immune protection against secondary NPHV infections. Horses were i.v. injected with NPHV containing plasma. Flow cytometric analysis was used to monitor immune cell frequencies and activation status. All infected horses became viremic after 1 or 2 wk and viremia could be detected in two horses for several weeks followed by a delayed seroconversion and viral clearance. Histopathological examinations of liver biopsies revealed mild, periportally accentuated infiltrations of lymphocytes, macrophages, and plasma cells with some horses displaying subclinical signs of hepatitis. Following viral challenge, an activation of equine immune responses was observed. Importantly, after a primary NPHV infection, horses were protected against rechallenge with the homologous as well as a distinct isolate with only minute amounts of circulating virus being detectable.hepatitis C virus | nonprimate hepacivirus | infection | immune protection | rechallenge H epatitis C virus (HCV) infections constitute a major global health problem with ∼130 million people being chronically infected (1). Once infected, 70-90% of individuals progress to chronicity, rendering HCV the leading cause of liver diseases, including liver fibrosis, cirrhosis, and hepatocellular carcinoma (2). HCV is a blood-borne, positive-stranded RNA virus classified to the family of Flaviviridae within the genus Hepacivirus. Seven different HCV genotypes and numerous subtypes have been described, which differ on the nucleotide level by ∼30-35% between different genotypes and maximally 30% between subtypes (3). Furthermore, within infected individuals the virus circulates as a population of closely related but distinct genomes (4). Recently, significant progress has been made regarding the treatment of HCV with the implementation of direct-acting antiviral (DAA) drugs, which can be administered as all-oral IFN-free therapeutics and should help to reduce the global burden of HCV infections (5). However, there are still many caveats, including high treatment costs and the risk of reinfection after successful therapy, which is a problem especially in patient populations with frequent exposure to HCV. Furthermore, the inadequacy of current HCV screening programs often results in late diagnosis of chronic HCV infection and subsequent proceeding to end-stage liver diseases (6). All of these challenges highlight the necessity for a prophylactic vaccine against HCV, ...

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An equine parvovirus-hepatitis (EqPV-H) has been recently identified in association with equine serum hepatitis, also known as Theiler’s disease. The disease was first described by Arnold Theiler in 1918 and is often observed with parenteral use of blood products in equines. However, natural ways of viral circulation and potential risk factors for transmission still remain unknown. In this study, we investigated the occurrence of EqPV-H infections in Thoroughbred horses in northern and western Germany and aimed to identify potential risk factors associated with viral infections. A total of 392 Thoroughbreds broodmares and stallions were evaluated cross-sectionally for the presence of anti-EqPV-H antibodies and EqPV-H DNA using a luciferase immunoprecipitation assay (LIPS) and a quantitative PCR, respectively. In addition, data regarding age, stud farm, breeding history, and international transportation history of each horse were collected and analysed. An occurrence of 7% EqPV-H DNA positive and 35% seropositive horses was observed in this study cohort. The systematic analysis of risk factors revealed that age, especially in the group of 11–15-year-old horses, and breeding history were potential risk factors that can influence the rate of EqPV-H infections. Subsequent phylogenetic analysis showed a high similarity on nucleotide level within the sequenced Thoroughbred samples. In conclusion, this study demonstrates circulating EqPV-H infections in Thoroughbred horses from central Europe and revealed age and breeding history as risk factors for EqPV-H infections.