title: The self-interaction of a nodavirus replicase is enhanced by mitochondrial membrane lipids.
abstract: RNA replication of positive-strand (+)RNA viruses requires the protein-protein interactions among viral replicases and the association of viral replicases with intracellular membranes. Protein A from Wuhan nodavirus (WhNV), which closely associate with mitochondrial membranes, is the sole replicase required for viral RNA replication. Here, we studied the direct effects of mitochondrial membrane lipids (MMLs) on WhNV protein A activity in vitro. Our investigations revealed the self-interaction of WhNV protein A is accomplished via two different patterns (i.e., homotypic and heterotypic self-interactions via different interfaces). MMLs stimulated the protein A self-interaction, and this stimulation exhibited selectivity for specific phospholipids. Moreover, we found that specific phospholipids differently favor the two self-interaction patterns. Furthermore, manipulating specific phospholipid metabolism affected protein A self-interaction and the activity of protein A to replicate RNA in cells. Taken together, our findings reveal the direct effects of membrane lipids on a nodaviral RNA replicase.
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei, China ; State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Qiu
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei, China.
authors.forename: Zhaowei
authors.initials: Z
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei, China.
authors.forename: Yongxiang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei, China.
authors.forename: Yajuan
authors.initials: Y
authors.lastname: Han
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Miao
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Qi
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei, China.
authors.forename: Hongjie
authors.initials: H
authors.lastname: Xia
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Li
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
authors.forename: Cheng-Feng
authors.initials: CF
authors.lastname: Qin
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei, China.
authors.forename: Yuanyang
authors.initials: Y
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Zhou
mesh_terms: D008563:Membrane Lipids / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism*; D030381:Nodaviridae / Q000502:physiology*; D010743:Phospholipids / Q000502:physiology; D012324:RNA-Dependent RNA Polymerase / Q000378:metabolism*; D014764:Viral Proteins / Q000378:metabolism; D014779:Virus Replication / Q000502:physiology
chemical_list: D008563:Membrane Lipids; D010743:Phospholipids; D014764:Viral Proteins; D012324:RNA-Dependent RNA Polymerase