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Viral proteins Cellular targets References HBs TLR2/JNK/IL-12 (Wang S, et al., 2013) TLR4/ERK, NF-κB/IL-18 (Cheng J, et al., 2005) TLR9/IFN-α (Vincent I E, et al., 2011; Xu Y, et al., 2009) HBe TLR2/MAL (Lang T, et al., 2011; Visvanathan K, et al., 2007) Polymerase RIG-Ⅰ, TLR3/TBK1, IKKɛ, DDX3/IFN-β (Wang H, et al., 2010; Yu S, et al., 2010) MITA/IFN-β (our unpublished data) IFN/JAK-STAT (Chen J, et al., 2013; Foster G R, et al., 1991) HBx RIG-Ⅰ, MDA5/MAVS/IFN-β (Kumar M, et al., 2011; Wei C, et al., 2010) Core/precore IFN/MxA (Fernandez M, et al., 2003) Table 1. HBV-encoded proteins that interferes with the innate immune signaling at multiple levels
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Strategies Anti-HBV effects References TLR ligands P2C/P3C (TLR2) Inhibits viral replication in vitro and in vivo (Zhang X, et al., 2012) poly (I:C) (TLR3) Reduces the levels of viral DNA, HBeAg and HBsAg in vitro and in vivo (Isogawa M, et al., 2005; Wu J, et al., 2007) GS-9620 (TLR7) Induces prolonged suppression of HBV in chronically infected chimpanzees (Lanford R E, et al., 2013) RLR ligands 5'-triphosphate RNAs Controls replication of hepatitis B virus (Ebert G, et al., 2011; Han Q, et al., 2011; Han Q, et al., 2011; Lan P, et al., 2013) PRR adaptors MyD88 Reduces the HBV mRNA and DNA (Guo H, et al., 2009; Li J, et al., 2010) TRIF MAVS IFN-related approaches anti-HBV ISGs MxA: suppresses the nucleocytoplasmic export of viral mRNA (Gordien E, et al., 2001) APOBEC3G: inhibits viral replication in deaminase activity-dependent and independent manners (Nguyen D H, et al., 2007; Turelli P, et al., 2004) ZAP: down-regulates the viral RNA (Mao R, et al., 2013) Exosomes containing antiviral factors Exosomes from nonparenchymal liver cells contributes to the IFN-induced antiviral response to HBV and restores the antiviral state in HBV-infected cells (Li J, et al., 2013) type Ⅲ IFNs Induces an intracellular IFN-α/β-like antiviral response through a receptor complex distinct from the IFN-α/β receptor (Pagliaccetti N E, et al., 2010; Robek M D, et al., 2005) Sequence-specific silencing RNAi Inhibits the viral gene expression (Chen Y, et al., 2008; Meng Z, et al., 2008) ZFP/ZFN Reduces the transcriptional activity of the viral genome (Cradick T J, et al., 2010; Zimmerman K A, et al., 2008) TALEN Inactivates the viral replication, cleaves the viral DNA in a site-specific manner (Chen J, et al., 2013) Combination Therapies RIG-Ⅰ ligands + siRNA Controls HBV replication more efficiently (Ebert G, et al., 2011; Han Q, et al., 2011) TALEN + IFN Results in an enhanced antiviral effect in vitro (Chen J, et al., 2013) Antivirals + vaccination Elicits sustained immunological control of chronic hepadnaviral infection in vivo (Kosinska A D, et al., 2013) Table 2. New control strategies for HBV infection by activating PRRs or inhibiting viral replication
Figure 1 个
Table 2 个
