Further characterization of bovine hepacivirus: Antibody response, course of infection, and host tropism.

Bovine hepacivirus (BovHepV) is a recently added member to the growing genus Hepacivirus within the family Flaviviridae. Animal hepaciviruses are rarely characterized so far. Apart from norway rat hepacivirus which represents a promising HCV surrogate model, only equine hepaciviruses have been studied to some extent. BovHepV has been initially identified in bovine samples and was shown to establish persistent infections in cattle. However, consequences of those chronic infections, humoral immune response and the possibility of an extended host spectrum have not been explored so far. Therefore, we here investigated (a) the presence of anti-NS3-antibodies and viral RNA in cattle herds in Germany, (b) the course of infection in cattle, and (c) the host tropism including zoonotic potential of bovine hepaciviruses. Our results show that 19.9% of investigated bovine serum samples had antibodies against BovHepV. In 8.2% of investigated samples, viral RNA was detected. Subsequent genetic analysis revealed a novel genetic cluster of BovHepV variants. For 25 selected cattle in a BovHepV positive herd the presence of viral genomic RNA was monitored over one year in two to three months intervals by RT-PCR in order to discriminate acute versus persistent infection. In persistently infected animals, no serum antibodies were detected. Biochemical analyses could not establish a link between BovHepV infection and liver injury. Apart from a single sample of a pig providing a positive reaction in the antibody test, neither BovHepV-specific antibodies nor viral RNA were detected in porcine, equine or human samples implying a strict host specificity of BovHepV.

Identification of a Novel Hepacivirus in Domestic Cattle from Germany.

UNLABELLED: Hepatitis C virus (HCV) continues to represent one of the most significant threats to human health. In recent years, HCV-related sequences have been found in bats, rodents, horses, and dogs, indicating a widespread distribution of hepaciviruses among animals. By applying unbiased high-throughput sequencing, a novel virus of the genus Hepacivirus was discovered in a bovine serum sample. De novo assembly yielded a nearly full-length genome coding for a polyprotein of 2,779 amino acids. Phylogenetic analysis confirmed that the virus represents a novel species within the genus Hepacivirus. Viral RNA screening determined that 1.6% (n = 5) of 320 individual animals and 3.2% (n = 5) of 158 investigated cattle herds in Germany were positive for bovine hepacivirus. Repeated reverse transcription-PCR (RT-PCR) analyses of animals from one dairy herd proved that a substantial percentage of cows were infected, with some of them being viremic for over 6 months. Clinical and postmortem examination revealed no signs of disease, including liver damage. Interestingly, quantitative RT-PCR from different organs and tissues, together with the presence of an miR-122 binding site in the viral genome, strongly suggests a liver tropism for bovine hepacivirus, making this novel virus a promising animal model for HCV infections in humans. IMPORTANCE: Livestock animals act as important sources for emerging pathogens. In particular, their large herd size and the existence of multiple ways of direct and food-borne infection routes emphasize their role as virus reservoirs. Apart from the search for novel viruses, detailed characterization of these pathogens is indispensable in the context of risk analysis. Here, we describe the identification of a novel HCV-like virus in cattle. In addition, determination of the prevalence and of the course of infection in cattle herds provides valuable insights into the biology of this novel virus. The results presented here form a basis for future studies targeting viral pathogenesis of bovine hepaciviruses and their potential to establish zoonotic infections.