https://www.mdpi.com/2076-393X/8/1/90/pdf

Hepatitis C Virus Vaccine: Challenges and Prospects.

One Health (OH) is a crucial concept, where the interference between humans, animals and the environment matters. This review article focusses on the role of horses in maintaining the health of humans and the environment. Horses' impact on environmental health includes their influence on soil and the biodiversity of animal and plant species. Nevertheless, the effect of horses is not usually linear and several factors like plant-animal coevolutionary history, climate and animal density play significant roles. The long history of the relationship between horses and humans is shaped by the service of horses in wars or even in mines. Moreover, horses were essential in developing the first antidote to cure diphtheria. Nowadays, horses do have an influential role in animal assisted therapy, in supporting livelihoods in low income countries and as a leisure partner. Horses are of relevance in the spillover of zoonotic and emerging diseases from wildlife to human (e.g., Hendra Virus), and in non-communicable diseases (e.g., post-traumatic osteoarthritis in horses and back pain in horse riders). Furthermore, many risk factors-such as climate change and antimicrobial resistance-threaten the health of both horses and humans. Finally, the horse is a valuable factor in sustaining the health of humans and the environment, and must be incorporated in any roadmap to achieve OH.

https://www.mdpi.com/2306-7381/7/1/28/pdf

Horses as a Crucial Part of One Health

Pegiviruses frequently cause persistent infection (as defined by >6 months), but unlike most other Flaviviridae members, no apparent clinical disease. Human pegivirus (HPgV, previously GBV-C) is detectable in 1-4% of healthy individuals and another 5-13% are seropositive. Some evidence for infection of bone marrow and spleen exists. Equine pegivirus 1 (EPgV-1) is not linked to disease, whereas another pegivirus, Theiler's disease-associated virus (TDAV), was identified in an outbreak of acute serum hepatitis (Theiler's disease) in horses. Although no subsequent reports link TDAV to disease, any association with hepatitis has not been formally examined. Here, we characterized EPgV-1 and TDAV tropism, sequence diversity, persistence and association with liver disease in horses. Among more than 20 tissue types, we consistently detected high viral loads only in serum, bone marrow and spleen, and viral RNA replication was consistently identified in bone marrow. PBMCs and lymph nodes, but not liver, were sporadically positive. To exclude potential effects of co-infecting agents in experimental infections, we constructed full-length consensus cDNA clones; this was enabled by determination of the complete viral genomes, including a novel TDAV 3' terminus. Clone derived RNA transcripts were used for direct intrasplenic inoculation of healthy horses. This led to productive infection detectable from week 2-3 and persisting beyond the 28 weeks of study. We did not observe any clinical signs of illness or elevation of circulating liver enzymes. The polyprotein consensus sequences did not change, suggesting that both clones were fully functional. To our knowledge, this is the first successful extrahepatic viral RNA launch and the first robust reverse genetics system for a pegivirus. In conclusion, equine pegiviruses are bone marrow tropic, cause persistent infection in horses, and are not associated with hepatitis. Based on these findings, it may be appropriate to rename the group of TDAV and related viruses as EPgV-2.

/pdf/equine-pegiviruses-cause-persistent-infection-of-bone-marrow-2x4rw5f3gn.pdf

Equine pegiviruses cause persistent infection of bone marrow and are not associated with hepatitis.

Pathogenesis, MicroRNA-122 Gene-Regulation, and Protective Immune Responses After Acute Equine Hepacivirus Infection.

Abstract Horses and other equids can be infected with several viruses of the family Flaviviridae, belonging to the genus Flavivirus and Hepacivirus. This consensus statement focuses on viruses with known occurrence in Europe, with the objective to summarize the current literature and formulate clinically relevant evidence‐based recommendations regarding clinical disease, diagnosis, treatment, and prevention. The viruses circulating in Europe include West Nile virus, tick‐borne encephalitis virus, Usutu virus, Louping ill virus and the equine hepacivirus. West Nile virus and Usutu virus are mosquito‐borne, while tick‐borne encephalitis virus and Louping ill virus are tick‐borne. The natural route of transmission for equine hepacivirus remains speculative. West Nile virus and tick‐borne encephalitis virus can induce encephalitis in infected horses. In the British Isle, rare equine cases of encephalitis associated with Louping ill virus are reported. In contrast, equine hepacivirus infections are associated with mild acute hepatitis and possibly chronic hepatitis. Diagnosis of flavivirus infections is made primarily by serology, although cross‐reactivity occurs. Virus neutralization testing is considered the gold standard to differentiate between flavivirus infections in horses. Hepacivirus infection is detected by serum or liver RT‐PCR. No direct antiviral treatment against flavi‐ or hepacivirus infections in horses is currently available and thus, treatment is supportive. Three vaccines against West Nile virus are licensed in the European Union. Geographic expansion of flaviviruses pathogenic for equids should always be considered a realistic threat, and it would be beneficial if their detection was included in surveillance programs.

European College of Equine Internal Medicine consensus statement on equine flaviviridae infections in Europe

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.

Chronic equine hepacivirus infection in an adult gelding with severe hepatopathy

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Chronic equine hepacivirus infection in an adult gelding with severe hepatopathy