Mouse models of acute and chronic hepacivirus infection

Eva K. Billerbeck, Raphael Wolfisberg, Ulrik Fahnøe, Jing W. Xiao, Corrine Quirk, Joseph M. Luna, John M. Cullen, Alex S. Hartlage, Luis Chiriboga, Kalpana Ghoshal, W. Ian Lipkin, Jens Bukh, Troels K.H. Scheel, Amit Kapoor, Charles M. Rice

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

An estimated 71 million people worldwide are infected with hepatitis C virus (HCV). The lack of small-animal models has impeded studies of antiviral immune mechanisms. Here we show that an HCV-related hepacivirus discovered in Norway rats can establish high-titer hepatotropic infections in laboratory mice with immunological features resembling those seen in human viral hepatitis. Whereas immune-compromised mice developed persistent infection, immune-competent mice cleared the virus within 3 to 5 weeks. Acute clearance was T cell dependent and associated with liver injury. Transient depletion of CD4+ T cells before infection resulted in chronic infection, characterized by high levels of intrahepatic regulatory T cells and expression of inhibitory molecules on intrahepatic CD8+ T cells. Natural killer cells controlled early infection but were not essential for viral clearance. This model may provide mechanistic insights into hepatic antiviral immunity, a prerequisite for the development of HCV vaccines.

Original languageEnglish (US)
Pages (from-to)204-208
Number of pages5
JournalScience
Volume357
Issue number6347
DOIs
StatePublished - Jul 14 2017
Externally publishedYes

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Hepacivirus
Infection
T-Lymphocytes
Hepatitis, Viral, Human
Antiviral Agents
Liver
Regulatory T-Lymphocytes
Natural Killer Cells
Immunity
Vaccines
Animal Models
Viruses
Wounds and Injuries

ASJC Scopus subject areas

  • General

Cite this

Billerbeck, E. K., Wolfisberg, R., Fahnøe, U., Xiao, J. W., Quirk, C., Luna, J. M., ... Rice, C. M. (2017). Mouse models of acute and chronic hepacivirus infection. Science, 357(6347), 204-208. https://doi.org/10.1126/science.aal1962

Mouse models of acute and chronic hepacivirus infection. / Billerbeck, Eva K.; Wolfisberg, Raphael; Fahnøe, Ulrik; Xiao, Jing W.; Quirk, Corrine; Luna, Joseph M.; Cullen, John M.; Hartlage, Alex S.; Chiriboga, Luis; Ghoshal, Kalpana; Lipkin, W. Ian; Bukh, Jens; Scheel, Troels K.H.; Kapoor, Amit; Rice, Charles M.

In: Science, Vol. 357, No. 6347, 14.07.2017, p. 204-208.

Research output: Contribution to journalArticle

Billerbeck, EK, Wolfisberg, R, Fahnøe, U, Xiao, JW, Quirk, C, Luna, JM, Cullen, JM, Hartlage, AS, Chiriboga, L, Ghoshal, K, Lipkin, WI, Bukh, J, Scheel, TKH, Kapoor, A & Rice, CM 2017, 'Mouse models of acute and chronic hepacivirus infection', Science, vol. 357, no. 6347, pp. 204-208. https://doi.org/10.1126/science.aal1962
Billerbeck EK, Wolfisberg R, Fahnøe U, Xiao JW, Quirk C, Luna JM et al. Mouse models of acute and chronic hepacivirus infection. Science. 2017 Jul 14;357(6347):204-208. https://doi.org/10.1126/science.aal1962
Billerbeck, Eva K. ; Wolfisberg, Raphael ; Fahnøe, Ulrik ; Xiao, Jing W. ; Quirk, Corrine ; Luna, Joseph M. ; Cullen, John M. ; Hartlage, Alex S. ; Chiriboga, Luis ; Ghoshal, Kalpana ; Lipkin, W. Ian ; Bukh, Jens ; Scheel, Troels K.H. ; Kapoor, Amit ; Rice, Charles M. / Mouse models of acute and chronic hepacivirus infection. In: Science. 2017 ; Vol. 357, No. 6347. pp. 204-208.
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