Interferons accelerate decay of replication-competent nucleocapsids of hepatitis B virus.
Alpha interferon (IFN-alpha) is an approved medication for chronic hepatitis B. Gamma interferon (IFN-gamma) is a key mediator of host antiviral immunity against hepatitis B virus (HBV) infection in vivo. However, the molecular mechanism by which these antiviral cytokines suppress HBV replication remains elusive. Using an immortalized murine hepatocyte (AML12)-derived cell line supporting tetracycline-inducible HBV replication, we show in this report that both IFN-alpha and IFN-gamma efficiently reduce the amount of intracellular HBV nucleocapsids. Furthermore, we provide evidence suggesting that the IFN-induced cellular antiviral response is able to distinguish and selectively accelerate the decay of HBV replication-competent nucleocapsids but not empty capsids in a proteasome-dependent manner. Our findings thus reveal a novel antiviral mechanism of IFNs and provide a basis for a better understanding of HBV pathobiology.
Xu
Chunxiao
C
Drexel Institute for Biotechnology and Virology Research, Department of Microbiology and Immunology, Drexel University College of Medicine, 3805 Old Easton Road, Doylestown, PA 18902, USA.
Guo
Haitao
H
Pan
Xiao-Ben
XB
Mao
Richeng
R
Yu
Wenquan
W
Xu
Xiaodong
X
Wei
Lai
L
Chang
Jinhong
J
Block
Timothy M
TM
Guo
Ju-Tao
JT
D000818:Animals; D002460:Cell Line; D006515:Hepatitis B virus / Q000276:immunology*; D022781:Hepatocytes / Q000821:virology; D016898:Interferon-alpha / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology*; D051379:Mice; D019251:Nucleocapsid / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism
D016898:Interferon-alpha; D007371:Interferon-gamma; D046988:Proteasome Endopeptidase Complex