title: Inhibition of hepatitis B virus replication by activation of the cGAS-STING pathway.
abstract: Cyclic GMP-AMP (cGAMP) synthase (cGAS) senses cytosolic DNA and catalyses synthesis of the second messenger cGAMP, which activates the downstream signalling adaptor protein STING, leading to the expression of type I interferons. Hepatitis B virus (HBV) is a small DNA virus, and the cGAS-STING pathway may inhibit HBV RNA synthesis and viral assembly in cell culture, but the exact roles of the cGAS pathway in the restriction of HBV replication in infection systems remain to be elucidated. In this study, replication of HBV was significantly inhibited both in cell culture and in vivo in a mouse model when the cGAS-STING pathway was activated by dsDNA or cGAMP. In contrast, the presence of enzymatically inactive cGAS mutant did not influence HBV replication. Moreover, knockdown of cGAS in human peripheral blood monocytes led to a higher level of intracellular HBV DNA. Collectively, our data indicate that the cGAS-STING pathway plays a role in the surveillance of HBV infection and may be exploited for development of novel anti-HBV strategies.
authors.affiliation: State Key Laboratory of Virology and Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: He
authors.affiliation: State Key Laboratory of Virology and Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, PR China.
authors.forename: Ruidong
authors.initials: R
authors.lastname: Hao
authors.affiliation: School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei 430072, PR China.
authors.forename: Dan
authors.initials: D
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Virology and Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, PR China.
authors.forename: Xing
authors.initials: X
authors.lastname: Liu
authors.affiliation: School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei 430072, PR China.
authors.forename: Shaoshuai
authors.initials: S
authors.lastname: Wu
authors.affiliation: College of Life Sciences, Wuhan Institute of Bioengineering, Wuhan, Hubei 430415, PR China.
authors.forename: Shuting
authors.initials: S
authors.lastname: Guo
authors.affiliation: School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei 430072, PR China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Virology and Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, PR China.
authors.forename: Po
authors.initials: P
authors.lastname: Tien
authors.affiliation: State Key Laboratory of Virology and Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, PR China.|School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei 430072, PR China.
authors.forename: Deyin
authors.initials: D
authors.lastname: Guo
mesh_terms: D000818:Animals; D005260:Female; D006509:Hepatitis B / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D006515:Hepatitis B virus / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009713:Nucleotidyltransferases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D019065:Virus Assembly; D014779:Virus Replication; D000099197:STING Protein; D000099235:Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase
chemical_list: D008565:Membrane Proteins; D009713:Nucleotidyltransferases; C532857:STING1 protein, human; D000099197:STING Protein; C578390:cGAS protein, human; D000099235:Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase