The inflammatory response is an attempt by a host to protect itself against injurious stimuli and initiate the tissue healing process [1,2]. Although the production of both pro-and anti-inflammatory mediators which occurs mainly within tissues is a systemic process,
TANG Hong1 & FU YangXin1,2 1 Key Laboratory of Infection and Immunity,Institute of Biophysics,Chinese Academy of Sciences,Beijing 100101,China
Summary： The type I interferon and IFNAR play an important role in hepatitis B virus （HBV） infection and anti-HBV therapy. However, its mechanism of action is still poorly understood. To gain more in- sights into the role of type I interferon and type I interferon receptor （IFNAR） in HBV infection, we established an HBV persistent replication IFNAR knockout （IFNAR-/-） mouse model and preliminarily applied this model. At first, the progeny of IFNAR-/- mouse was reproduced. Then hydrodynamic injec- tion with pAAV/HBV1.2 plasmid was conducted to establish the persistent HBV replication IFNAR-/- mouse model. At last, we applied this model to evaluate the effect of nucleoside analogues entecavir （ETV） on HBV replication. It was found that there was no difference in the serum HBsAg and HBeAg levels and HBcAg expression in the liver tissue between the ETV treated groups and normal saline （NS） treated group, but the serum HBV DNA levels were significantly suppressed 10, 25, 40 and 55 days af- ter the ETV treatment [P=0.035, P=0.00, P=0.149 and P=-0.084, IFNAR knockout （KO） control group vs. C57BL/6 ETV groups, respectively; P=0.081, P=0.001, P=0.243 and P=-0.147, IFNAR KO control group vs. IFNAR KO ETV groups, respectively]. Interestingly, there was no difference in serum HBV DNA levels between the ETV treated IFNAR/- and C57BL/6 mice. This result suggests that HBV sup- pression during ETV treatments doesn＇t depend on type Ⅰinterferon and IFNAR. Collectively, persis- tent HBV replication IFNAR/ mouse model that we established is a useful and convenient tool to detect the function of the type Ⅰ interferon and IFNAR in HBV infection and anti-HBV treatments.
One group of Bcl-2 protein family,which shares only the BH3 domain(BH3-only),is critically involved in the regulation of programmed cell death.Herein we demonstrated a novel human BH3-only protein(designated as Bop)which could induce apoptosis in a BH3 domain-dependent manner.Further analysis indicated that Bop mainly localized to mitochondria and used its BH3 domain to contact the loop regions of voltage dependent anion channel 1(VDAC1)in the outer mitochondrial membrane.In addition,purified Bop protein induced the loss of mitochondrial transmembrane potential(ΔΨm)and the release of cytochrome c.Furthermore,Bop used its BH3 domain to contact pro-survival Bcl-2 family members(Bcl-2,Bcl-XL,Mcl-1,A1 and Bcl-w),which could inhibit Bop-induced apoptosis.Bop would be constrained by pro-survival Bcl-2 proteins in resting cells,because Bop became released from phosphorylated Bcl-2 induced by microtubule-interfering agent like vincristine(VCR).Indeed,knockdown experiments indicated that Bop was partially required for VCR induced cell death.Finally,Bop might need to function through Bak and Bax,likely by releasing Bak from Bcl-XL sequestration.In conclusion,Bop may be a novel BH3-only factor that can engage with the regulatory network of Bcl-2 family members to process intrinsic apoptotic signaling.
