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.

Background Equine parvovirus‐hepatitis (EqPV‐H) research is in its infancy. Information regarding prevalence, geographical distribution, genetic diversity, pathogenesis and risk factors enhances understanding of this potentially fatal infection. Objectives Determining the prevalence of EqPV‐H in Austrian equids. Investigating factors increasing probability of infection, liver‐associated biochemistry parameters, concurrent equine hepacivirus (EqHV) infection and phylogenetic analysis of Austrian EqPV‐H variants. Study design Cross‐sectional study. Methods Sera from 259 horses and 13 donkeys in Austria were analysed for anti‐EqPV‐H VP1‐specific antibodies by luciferase immunoprecipitation system (LIPS) and EqPV‐H DNA by nested polymerase chain reaction (PCR). Associations between infection status, sex and age were described. Glutamate dehydrogenase (GLDH), gamma‐glutamyl transferase (GGT), bile acids and albumin concentrations were compared between horses with active infection and PCR‐negative horses. PCR targeting partial EqPV‐H NS1 was performed and phylogenetic analysis of Austrian EqPV‐H variants was conducted. Complete coding sequences (CDS) of four Austrian variants were determined by next‐generation sequencing (NGS) and compared with published sequences. Results Horses' EqPV‐H seroprevalence was 30.1% and DNA prevalence was 8.9%. One horse was co‐infected with EqHV. Significantly, higher probability of active EqPV‐H infection was identified in 16‐ to 31‐year‐old horses, compared with 1‐ to 8‐year‐old horses (P = 0.002; OR = 8.19; 95% CI = 1.79 to 37.50) and 9‐ to 15‐year‐old horses (P = 0.03; OR = 2.96; 95% CI = 1.08 to 8.17). Liver‐associated plasma parameters were not significantly different between horses with active infection and controls. Austrian EqPV‐H variants revealed high similarity to sequences worldwide. No evidence of EqPV‐H was detected in donkeys. Main limitations Equids’ inclusion depended upon owner consent. There was only one sampling point per animal and the sample of donkeys was small. Conclusions EqPV‐H antibodies and DNA are frequently detected in Austrian horses, without associated hepatitis in horses with active infection. The risk of active EqPV‐H infection increases with increasing age. Phylogenetic evidence supports close relation of EqPV‐H variants globally, including Austrian variants.

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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. This disease was first described by Arnold Theiler in 1918 and is often observed after applications with blood products in equines. So far, the virus has only been described in the USA and China. In this study, we evaluated the presence of EqPV-H in several commercial serum samples to assess the potential risk of virus transmission by equine serum-based products for medical and research applications. In 11 out of 18 commercial serum samples, EqPV-H DNA was detectable with a viral load up to 105 copies/mL. The same serum batches as well as three additional samples were also positive for antibodies against the EqPV-H VP1 protein. The countries of origin with detectable viral genomes included the USA, Canada, New Zealand, Italy, and Germany, suggesting a worldwide distribution of EqPV-H. Phylogenetic analysis of the EqPV-H NS1 sequence in commercial serum samples revealed high similarities in viral sequences from different geographical areas. As horse sera are commonly used for the production of anti-sera, which are included in human and veterinary medical products, these results implicate the requirement for diagnostic tests to prevent EqPV-H transmission.

Hepatitis C virus (HCV) has no animal reservoir, infecting only humans. To investigate species barrier determinants limiting infection of rodents, murine liver complementary DNA library screening was performed, identifying transmembrane proteins Cd302 and Cr1l as potent restrictors of HCV propagation. Combined ectopic expression in human hepatoma cells impeded HCV uptake and cooperatively mediated transcriptional dysregulation of a noncanonical program of immunity genes. Murine hepatocyte expression of both factors was constitutive and not interferon inducible, while differences in liver expression and the ability to restrict HCV were observed between the murine orthologs and their human counterparts. Genetic ablation of endogenous Cd302 expression in human HCV entry factor transgenic mice increased hepatocyte permissiveness for an adapted HCV strain and dysregulated expression of metabolic process and host defense genes. These findings highlight human-mouse differences in liver-intrinsic antiviral immunity and facilitate the development of next-generation murine models for preclinical testing of HCV vaccine candidates.

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.

Yellow fever virus (YFV) represents a re-emerging zoonotic pathogen, transmitted by mosquito vectors to humans from primate reservoirs. Sporadic outbreaks of YFV occur in endemic tropical regions, causing a viral hemorrhagic fever (VHF) associated with high mortality rates. Despite a highly effective vaccine, no antiviral treatments currently exist. Therefore, YFV represents a neglected tropical disease and is chronically understudied, with many aspects of YFV biology incompletely defined including host range, host–virus interactions and correlates of host immunity and pathogenicity. In this article, we review the current state of YFV research, focusing on the viral lifecycle, host responses to infection, species tropism and the success and associated limitations of the YFV-17D vaccine. In addition, we highlight the current lack of available treatments and use publicly available sequence and structural data to assess global patterns of YFV sequence diversity and identify potential drug targets. Finally, we discuss how technological advances, including real-time epidemiological monitoring of outbreaks using next-generation sequencing and CRISPR/Cas9 modification of vector species, could be utilized in future battles against this re-emerging pathogen which continues to cause devastating disease.

The genealogy of the hepatitis C virus (HCV) and the genus Hepacivirus remains elusive despite numerous recently discovered animal hepaciviruses (HVs). Viruses from evolutionarily ancient mammals might elucidate the HV macro-evolutionary patterns. Here, we investigated sixty-seven two-toed and nine three-toed sloths from Costa Rica for HVs using molecular and serological tools. A novel sloth HV was detected by reverse transcription polymerase chain reaction (RT-PCR) in three-toed sloths (2/9, 22.2%; 95% confidence interval (CI), 5.3–55.7). Genomic characterization revealed typical HV features including overall polyprotein gene structure, a type 4 internal ribosomal entry site in the viral 5′-genome terminus, an A–U-rich region and X-tail structure in the viral 3′-genome terminus. Different from other animal HVs, HV seropositivity in two-toed sloths was low at 4.5 per cent (3/67; CI, 1.0–12.9), whereas the RT-PCR-positive three-toed sloths were seronegative. Limited cross-reactivity of the serological assay implied exposure of seropositive two-toed sloths to HVs of unknown origin and recent infections in RT-PCR-positive animals preceding seroconversion. Recent infections were consistent with only 9 nucleotide exchanges between the two sloth HVs, located predominantly within the E1/E2 encoding regions. Translated sequence distances of NS3 and NS5 proteins and host comparisons suggested that the sloth HV represents a novel HV species. Event- and sequence distance-based reconciliations of phylogenies of HVs and of their hosts revealed complex macro-evolutionary patterns, including both long-term evolutionary associations and host switches, most strikingly from rodents into sloths. Ancestral state reconstructions corroborated rodents as predominant sources of HV host switches during the genealogy of extant HVs. Sequence distance comparisons, partial conservation of critical amino acid residues associated with HV entry and selection pressure signatures of host genes encoding entry and antiviral protein orthologs were consistent with HV host switches between genetically divergent mammals, including the projected host switch from rodents into sloths. Structural comparison of HCV and sloth HV E2 proteins suggested conserved modes of hepaciviral entry. Our data corroborate complex macro-evolutionary patterns shaping the genus Hepacivirus, highlight that host switches are possible across highly diverse host taxa, and elucidate a prominent role of rodent hosts during the Hepacivirus genealogy.