Immune protection against reinfection with nonprimate hepacivirus.

Pfänder, Stephanie; Walter, Stephanie; Grabski, Elena; Todt, Daniel; Bruening, Janina; Romero-Brey, Inés; Gather, Theresa; Brown, Richard J P; Hahn, Kerstin; Puff, Christina; Pfankuche, Vanessa M; Hansmann, Florian; Postel, Alexander; Becher, Paul; Thiel, Volker Earl; Kalinke, Ulrich; Wagner, Bettina; Bartenschlager, Ralf; Baumgärtner, Wolfgang; Feige, Karsten; ... (2017). Immune protection against reinfection with nonprimate hepacivirus. Proceedings of the National Academy of Sciences of the United States of America - PNAS, 114(12), E2430-E2439. National Academy of Sciences NAS 10.1073/pnas.1619380114

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Virology and Immunology
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP)
05 Veterinary Medicine > Research Foci > Host-Pathogen Interaction

UniBE Contributor:

Pfänder, Stephanie and Thiel, Volker Earl

Subjects:

600 Technology > 630 Agriculture
500 Science > 570 Life sciences; biology

ISSN:

0027-8424

Publisher:

National Academy of Sciences NAS

Language:

English

Submitter:

Achim Braun Parham

Date Deposited:

15 May 2018 14:32

Last Modified:

15 May 2018 14:42

Publisher DOI:

10.1073/pnas.1619380114

PubMed ID:

28275093

Uncontrolled Keywords:

hepatitis C virus immune protection infection nonprimate hepacivirus rechallenge

BORIS DOI:

10.7892/boris.112061

URI:

https://boris.unibe.ch/id/eprint/112061

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