title: 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.
authors.affiliation: 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.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Pfaender
authors.affiliation: 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.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Walter
authors.affiliation: Institute for Experimental Infection Research, Twincore Centre for Experimental and Clinical Infection Research, MHH-HZI, 30625 Hannover, Germany.
authors.forename: Elena
authors.initials: E
authors.lastname: Grabski
authors.affiliation: 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.
authors.forename: Daniel
authors.initials: D
authors.lastname: Todt
authors.affiliation: 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.
authors.forename: Janina
authors.initials: J
authors.lastname: Bruening
authors.affiliation: Department of Infectious Diseases, Molecular Virology, Heidelberg University, 69120 Heidelberg, Germany.
authors.forename: Inés
authors.initials: I
authors.lastname: Romero-Brey
authors.affiliation: Clinic for Horses, University of Veterinary Medicine Hannover, 30559 Hannover, Germany.
authors.forename: Theresa
authors.initials: T
authors.lastname: Gather
authors.affiliation: 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.
authors.forename: Richard J P
authors.initials: RJ
authors.lastname: Brown
authors.affiliation: Department of Pathology, University of Veterinary Medicine Hannover, 30559 Hannover, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Hahn
authors.affiliation: Department of Pathology, University of Veterinary Medicine Hannover, 30559 Hannover, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Puff
authors.affiliation: Department of Pathology, University of Veterinary Medicine Hannover, 30559 Hannover, Germany.
authors.forename: Vanessa M
authors.initials: VM
authors.lastname: Pfankuche
authors.affiliation: Department of Pathology, University of Veterinary Medicine Hannover, 30559 Hannover, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Hansmann
authors.affiliation: Institute of Virology, University of Veterinary Medicine Hannover, 30559 Hannover, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Postel
authors.affiliation: Institute of Virology, University of Veterinary Medicine Hannover, 30559 Hannover, Germany.
authors.forename: Paul
authors.initials: P
authors.lastname: Becher
authors.affiliation: 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.
authors.forename: Volker
authors.initials: V
authors.lastname: Thiel
authors.affiliation: Institute for Experimental Infection Research, Twincore Centre for Experimental and Clinical Infection Research, MHH-HZI, 30625 Hannover, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Kalinke
authors.affiliation: Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853.
authors.forename: Bettina
authors.initials: B
authors.lastname: Wagner
authors.affiliation: 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.
authors.forename: Ralf
authors.initials: R
authors.lastname: Bartenschlager
authors.affiliation: Department of Pathology, University of Veterinary Medicine Hannover, 30559 Hannover, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Baumgärtner
authors.affiliation: Clinic for Horses, University of Veterinary Medicine Hannover, 30559 Hannover, Germany.
authors.forename: Karsten
authors.initials: K
authors.lastname: Feige
authors.affiliation: 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.
authors.forename: Thomas
authors.initials: T
authors.lastname: Pietschmann
authors.affiliation: Clinic for Horses, University of Veterinary Medicine Hannover, 30559 Hannover, Germany; eike.steinmann@twincore.de jessika.cavalleri@tiho-hannover.de.
authors.forename: Jessika M V
authors.initials: JM
authors.lastname: Cavalleri
authors.affiliation: 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.
authors.forename: Eike
authors.initials: E
authors.lastname: Steinmann
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D004195:Disease Models, Animal; D016174:Hepacivirus / Q000145:classification / Q000235:genetics / Q000502:physiology*; D006526:Hepatitis C / Q000276:immunology / Q000517:prevention & control / Q000662:veterinary* / Q000821:virology; D006734:Horse Diseases / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D006736:Horses; D006801:Humans; D010802:Phylogeny; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000914:Antibodies, Viral
keywords: hepatitis C virus; immune protection; infection; nonprimate hepacivirus; rechallenge