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Proceedings of the National Academy of Sciences of the United States of America2017; 114(12); E2430-E2439; doi: 10.1073/pnas.1619380114

Immune protection against reinfection with nonprimate hepacivirus.

Abstract: 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.
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Publication Date: 2017-03-08 PubMed ID: 28275093PubMed Central: PMC5373355DOI: 10.1073/pnas.1619380114Google Scholar: Lookup
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  • U.S. Gov't
  • Non-P.H.S.

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The study investigates how horses’ immune systems respond to and protect against subsequent infections of nonprimate hepacivirus (NPHV), a virus very similar to human Hepatitis C Virus (HCV). Through experimental infection and subsequent re-infection, results showed the horses’ immune systems were activated and effective in defending against the virus.

Article Explanation and Detailed Discussion

  • The Hepatitis C virus (HCV), which is restricted in infecting only humans and chimpanzees, has a close homolog in the nonprimate hepacivirus (NPHV) found in horses. This similarity offers an opportunity to study hepacivirus infections within their natural hosts (horses), which can reveal information about how the same might happen in humans.
  • The study aimed to understand the equine (horse) immune responses to NPHV by initiating an experimental NPHV infection in the horses, and later reexposing them to the virus. The goal was to evaluate whether these horses, once exposed to the virus, could build immunity and protect themselves against subsequent infections.
  • Flow cytometric analysis, a technique used to measure physical and chemical characteristics of cells, was used to monitor changes in immune cell frequencies and activation status.
  • All the horses that were intravenously injected with NPHV containing plasma turned out to be viremic (presence of virus in the bloodstream) after 1 or 2 weeks. However, viremia continued to be detected in a couple of horses for several weeks which was followed by a delayed seroconversion, the period during which a specific antibody develops and becomes detectable in the blood, and subsequent viral clearance.
  • Liver biopsies showed mild infiltrations of lymphocytes (white blood cells that play a key role in immune response), macrophages (a type of white blood cell that consumes foreign substances), and plasma cells (cells that produce antibodies). Some horses displayed subclinical signs of hepatitis – mild and not severe symptoms.
  • Crucially, after the initial NPHV infection, when rechallenged with the same virus, the horses were protected. Notably, this immunity extended to a different strain of the virus, with only small amounts of circulating virus detectable.

This study contributes to understanding HCV by studying its homolog in horses, NPHV. The immune response observed in horses could be indicative of the potential human immune response, offering insights into virus control, pathogenesis, and possible vaccination strategies.

Cite This Article

APA
Pfaender S, Walter S, Grabski E, Todt D, Bruening J, Romero-Brey I, Gather T, Brown RJ, Hahn K, Puff C, Pfankuche VM, Hansmann F, Postel A, Becher P, Thiel V, Kalinke U, Wagner B, Bartenschlager R, Baumgärtner W, Feige K, Pietschmann T, Cavalleri JM, Steinmann E. (2017). Immune protection against reinfection with nonprimate hepacivirus. Proc Natl Acad Sci U S A, 114(12), E2430-E2439. https://doi.org/10.1073/pnas.1619380114

Publication

Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
NlmUniqueID: 7505876
Country: United States
Language: English
Volume: 114
Issue: 12
Pages: E2430-E2439

Researcher Affiliations

Pfaender, Stephanie
  • 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.
  • Department of Infectious Diseases and Pathobiology, University of Bern, 3012 Bern, Switzerland.
  • Federal Department of Home Affairs, Institute of Virology and Immunology, 3012 Bern and 3147 Mittelhäusern, Switzerland.
Walter, Stephanie
  • 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, Elena
  • Institute for Experimental Infection Research, Twincore Centre for Experimental and Clinical Infection Research, MHH-HZI, 30625 Hannover, Germany.
Todt, Daniel
  • 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, Janina
  • 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, Inés
  • Department of Infectious Diseases, Molecular Virology, Heidelberg University, 69120 Heidelberg, Germany.
Gather, Theresa
  • Clinic for Horses, University of Veterinary Medicine Hannover, 30559 Hannover, Germany.
Brown, Richard J P
  • 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, Kerstin
  • Department of Pathology, University of Veterinary Medicine Hannover, 30559 Hannover, Germany.
Puff, Christina
  • Department of Pathology, University of Veterinary Medicine Hannover, 30559 Hannover, Germany.
Pfankuche, Vanessa M
  • Department of Pathology, University of Veterinary Medicine Hannover, 30559 Hannover, Germany.
Hansmann, Florian
  • Department of Pathology, University of Veterinary Medicine Hannover, 30559 Hannover, Germany.
Postel, Alexander
  • Institute of Virology, University of Veterinary Medicine Hannover, 30559 Hannover, Germany.
Becher, Paul
  • Institute of Virology, University of Veterinary Medicine Hannover, 30559 Hannover, Germany.
Thiel, Volker
  • Department of Infectious Diseases and Pathobiology, University of Bern, 3012 Bern, Switzerland.
  • Federal Department of Home Affairs, Institute of Virology and Immunology, 3012 Bern and 3147 Mittelhäusern, Switzerland.
Kalinke, Ulrich
  • Institute for Experimental Infection Research, Twincore Centre for Experimental and Clinical Infection Research, MHH-HZI, 30625 Hannover, Germany.
Wagner, Bettina
  • Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853.
Bartenschlager, Ralf
  • Department of Infectious Diseases, Molecular Virology, Heidelberg University, 69120 Heidelberg, Germany.
  • Division of Virus-Associated Carcinogenesis, German Cancer Research Center, 69120 Heidelberg, Germany.
  • German Center for Infection Research, Heidelberg University, 69117 Heidelberg, Germany.
Baumgärtner, Wolfgang
  • Department of Pathology, University of Veterinary Medicine Hannover, 30559 Hannover, Germany.
Feige, Karsten
  • Clinic for Horses, University of Veterinary Medicine Hannover, 30559 Hannover, Germany.
Pietschmann, Thomas
  • 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, Jessika M V
  • Clinic for Horses, University of Veterinary Medicine Hannover, 30559 Hannover, Germany; eike.steinmann@twincore.de jessika.cavalleri@tiho-hannover.de.
Steinmann, Eike
  • 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.

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

Conflict of Interest Statement

The authors declare no conflict of interest.

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