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2016 ; 7
(42
): 68179-68193
Nephropedia Template TP
gab.com Text
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English Wikipedia
Interferon-stimulated gene of 20 kDa protein (ISG20) degrades RNA of hepatitis B
virus to impede the replication of HBV in vitro and in vivo
#MMPMID27626689
Leong CR
; Funami K
; Oshiumi H
; Mengao D
; Takaki H
; Matsumoto M
; Aly HH
; Watashi K
; Chayama K
; Seya T
Oncotarget
2016[Oct]; 7
(42
): 68179-68193
PMID27626689
show ga
Hepatitis B virus (HBV) barely induces host interferon (IFN)-stimulated genes
(ISGs), which allows efficient HBV replication in the immortalized mouse
hepatocytes as per human hepatocytes. Here we found that transfection of Isg20
plasmid robustly inhibits the HBV replication in HBV-infected hepatocytes
irrespective of IRF3 or IFN promoter activation. Transfection of Isg20 is thus
effective to eradicate HBV in the infected hepatocytes. Transfection of HBV
genome or ?-stem of HBV pgRNA (active pgRNA moiety) failed to induce Isg20 in the
hepatocytes, while control polyI:C (a viral dsRNA analogue mimic) activated MAVS
pathway leading to production of type I IFN and then ISGsg20 via the IFN-?/?
receptor (IFNAR). Consistently, addition of IFN-? induced Isg20 and partially
suppressed HBV replication in hepatocytes. Chasing HBV RNA, DNA and proteins by
blotting indicated that ISG20 expression decreased HBV RNA and replicative DNA in
HBV-transfected cells, which resulted in low HBs antigen production and virus
titer. The exonuclease domains of ISG20 mainly participated in HBV-RNA decay. In
vivo hydrodynamic injection, ISG20 was crucial for suppressing HBV replication
without degrading host RNA in the liver. Taken together, ISG20 acts as an innate
anti-HBV effector that selectively degrades HBV RNA and blocks replication of
infectious HBV particles. ISG20 would be a critical effector for ameliorating
chronic HBV infection in the IFN therapy.