Immune protection against reinfection with nonprimate hepacivirus.

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.

Vertical transmission of hepatitis C virus-like non-primate hepacivirus in horses.

Non-primate hepacivirus (NPHV), a recently discovered hepatotropic virus infecting horses, is phylogenetically the closest known homologue of hepatitis C virus (HCV). The main route for acquiring HCV infection in childhood is vertical transmission. However, nothing is known about the natural mode of transmission for NPHV. To investigate the possibility of vertically transmitted NPHV infection in horses, 20 Thoroughbred broodmares and their foals were monitored during foaling season 2015 until 6 months post-partum. Prepartal serum was taken from the mares, and during foaling umbilical cord blood and colostrum samples were collected. Postnatal serum samples were taken from the foals after delivery. In addition, serum was taken at 3 and 6 months after foaling from all mares and foals. Samples were analysed for the presence of NPHV RNA by quantitative real-time PCR and for the presence of anti-NPHV NS3 antibodies by luciferase immunoprecipitation system. Identified NPHV isolates were sequenced and phylogenetic analysis of the viral glycoproteins was used to track the course of naturally occurring infections and the circulation of distinct isolates within the herd. At parturition, 16 mares were seropositive, including four viraemic mares. Vertical transmission occurred in one of these four mare-foal pairs. Interestingly, NPHV isolates of newly infected foals and mares after 3 and 6 months cluster in their respective pasture herds suggesting another horizontal route of transmission.

Acute and chronic infections with nonprimate hepacivirus in young horses.

The recently discovered nonprimate hepacivirus (NPHV) naturally infects horses and is the closest known homolog of hepatitis C virus to date. Within a follow-up study acute field infections were monitored in four young Thoroughbred horses until the ages of 12-13 months. Serum samples were analyzed for the presence of NPHV RNA and anti-NPHV NS3 antibodies and liver specific parameters were evaluated. The four young horses were not able to clear infection, but remained chronically infected for the entire monitored time period despite the presence of NPHV specific antibodies.