Immune protection against reinfection with nonprimate hepacivirus

Proc Natl Acad Sci U S A. 2017 Mar 21;114(12):E2430-E2439. doi: 10.1073/pnas.1619380114. Epub 2017 Mar 8.


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.

Keywords: hepatitis C virus; immune protection; infection; nonprimate hepacivirus; rechallenge.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antibodies, Viral / immunology
  • Disease Models, Animal
  • Hepacivirus / classification
  • Hepacivirus / genetics
  • Hepacivirus / physiology*
  • Hepatitis C / immunology
  • Hepatitis C / prevention & control
  • Hepatitis C / veterinary*
  • Hepatitis C / virology
  • Horse Diseases / immunology*
  • Horse Diseases / prevention & control
  • Horse Diseases / virology
  • Horses
  • Humans
  • Phylogeny
  • T-Lymphocytes / immunology


  • Antibodies, Viral

Associated data

  • GENBANK/KY124246
  • GENBANK/KY124248