Mouse models of acute and chronic hepacivirus infection
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Mouse models of acute and chronic hepacivirus infection. / Billerbeck, Eva; 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, 2017, p. 204-208.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - Mouse models of acute and chronic hepacivirus infection
AU - Billerbeck, Eva
AU - Wolfisberg, Raphael
AU - Fahnøe, Ulrik
AU - Xiao, Jing W.
AU - Quirk, Corrine
AU - Luna, Joseph M
AU - Cullen, John M
AU - Hartlage, Alex S.
AU - Chiriboga, Luis
AU - Ghoshal, Kalpana
AU - Lipkin, W Ian
AU - Bukh, Jens
AU - Scheel, Troels K.H.
AU - Kapoor, Amit
AU - Rice, Charles M
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
U2 - 10.1126/science.aal1962
DO - 10.1126/science.aal1962
M3 - Journal article
C2 - 28706073
AN - SCOPUS:85025478531
VL - 357
SP - 204
EP - 208
JO - Science
JF - Science
SN - 0036-8075
IS - 6347
ER -
ID: 182122953