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Immune protection against reinfection with nonprimate hepacivirus.

  • Pfaender S Institute for Experimental Virology, Twincore Centre for Experimental and Clinical Infection Research, Medical School Hannover (MHH)-Helmholtz Centre for Infection Research (HZI), 30625 Hannover, Germany.
  • Walter S Institute for Experimental Virology, Twincore Centre for Experimental and Clinical Infection Research, Medical School Hannover (MHH)-Helmholtz Centre for Infection Research (HZI), 30625 Hannover, Germany.
  • Grabski E Institute for Experimental Infection Research, Twincore Centre for Experimental and Clinical Infection Research, MHH-HZI, 30625 Hannover, Germany.
  • Todt D Institute for Experimental Virology, Twincore Centre for Experimental and Clinical Infection Research, Medical School Hannover (MHH)-Helmholtz Centre for Infection Research (HZI), 30625 Hannover, Germany.
  • Bruening J Institute for Experimental Virology, Twincore Centre for Experimental and Clinical Infection Research, Medical School Hannover (MHH)-Helmholtz Centre for Infection Research (HZI), 30625 Hannover, Germany.
  • Romero-Brey I Department of Infectious Diseases, Molecular Virology, Heidelberg University, 69120 Heidelberg, Germany.
  • Gather T Clinic for Horses, University of Veterinary Medicine Hannover, 30559 Hannover, Germany.
  • Brown RJ Institute for Experimental Virology, Twincore Centre for Experimental and Clinical Infection Research, Medical School Hannover (MHH)-Helmholtz Centre for Infection Research (HZI), 30625 Hannover, Germany.
  • Hahn K Department of Pathology, University of Veterinary Medicine Hannover, 30559 Hannover, Germany.
  • Puff C Department of Pathology, University of Veterinary Medicine Hannover, 30559 Hannover, Germany.
  • Pfankuche VM Department of Pathology, University of Veterinary Medicine Hannover, 30559 Hannover, Germany.
  • Hansmann F Department of Pathology, University of Veterinary Medicine Hannover, 30559 Hannover, Germany.
  • Postel A Institute of Virology, University of Veterinary Medicine Hannover, 30559 Hannover, Germany.
  • Becher P Institute of Virology, University of Veterinary Medicine Hannover, 30559 Hannover, Germany.
  • Thiel V Department of Infectious Diseases and Pathobiology, University of Bern, 3012 Bern, Switzerland.
  • Kalinke U Institute for Experimental Infection Research, Twincore Centre for Experimental and Clinical Infection Research, MHH-HZI, 30625 Hannover, Germany.
  • Wagner B Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853.
  • Bartenschlager R Department of Infectious Diseases, Molecular Virology, Heidelberg University, 69120 Heidelberg, Germany.
  • Baumgärtner W Department of Pathology, University of Veterinary Medicine Hannover, 30559 Hannover, Germany.
  • Feige K Clinic for Horses, University of Veterinary Medicine Hannover, 30559 Hannover, Germany.
  • Pietschmann T Institute for Experimental Virology, Twincore Centre for Experimental and Clinical Infection Research, Medical School Hannover (MHH)-Helmholtz Centre for Infection Research (HZI), 30625 Hannover, Germany.
  • Cavalleri JM Clinic for Horses, University of Veterinary Medicine Hannover, 30559 Hannover, Germany; eike.steinmann@twincore.de jessika.cavalleri@tiho-hannover.de.
  • Steinmann E Institute for Experimental Virology, Twincore Centre for Experimental and Clinical Infection Research, Medical School Hannover (MHH)-Helmholtz Centre for Infection Research (HZI), 30625 Hannover, Germany; eike.steinmann@twincore.de jessika.cavalleri@tiho-hannover.de.
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  • 2017-03-10
Published in:
  • Proceedings of the National Academy of Sciences of the United States of America. - 2017
hepatitis C virus
immune protection
infection
nonprimate hepacivirus
rechallenge
Animals
Antibodies, Viral
Disease Models, Animal
Hepacivirus
Hepatitis C
Horse Diseases
Horses
Humans
Phylogeny
T-Lymphocytes
English 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.
Language
  • English
Open access status
bronze
Identifiers
Persistent URL
https://sonar.ch/global/documents/247283
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