title: HA Triggers the Switch from MEK1 SUMOylation to Phosphorylation of the ERK Pathway in Influenza A Virus-Infected Cells and Facilitates Its Infection.
abstract: Several post-translational modifications in host cells are hijacked by pathogens to facilitate their propagation. A number of components of the influenza virus have been reported to be modified by small ubiquitin-like modifier (SUMO) proteins during infection. We hypothesized that the MAPK/ERK pathway could be modified by SUMO1 because the SUMOylation of MEK1 was quickly eliminated after influenza A virus infection. We identified host cell MEK1 as a target of SUMO1 through LC/MS/MS, and enhanced MEK1 SUMOylation inhibited the infection of the virus, while inhibition of host cell MEK1 SUMOylation facilitated virus propagation. Further investigation demonstrated that the MAPK/ERK pathway is downregulated by MEK1 SUMOylation, which is inhibited by influenza virus infection. Furthermore, membrane accumulation of hemagglutinin promoted MEK1 phosphorylation and gradually abrogated the MEK1 SUMOylation. Taken together, we report a possible mechanism in which HA may trigger the ERK pathway in influenza A virus-infected cells as the switch from MEK1 SUMOylation to phosphorylation, facilitating virus infection.
authors.affiliation: Key Lab of Animal Ecology and Conservation Biology and National Research Center for Wildlife-borne Diseases, Institute of Zoology, Chinese Academy of Sciences Beijing, China.
authors.forename: Chengmin
authors.initials: C
authors.lastname: Wang
authors.affiliation: Key Lab of Animal Ecology and Conservation Biology and National Research Center for Wildlife-borne Diseases, Institute of Zoology, Chinese Academy of Sciences Beijing, China.
authors.forename: Huimin
authors.initials: H
authors.lastname: Liu
authors.affiliation: Key Lab of Animal Ecology and Conservation Biology and National Research Center for Wildlife-borne Diseases, Institute of Zoology, Chinese Academy of Sciences Beijing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Luo
authors.affiliation: Key Lab of Animal Ecology and Conservation Biology and National Research Center for Wildlife-borne Diseases, Institute of Zoology, Chinese Academy of Sciences Beijing, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.affiliation: Key Lab of Animal Ecology and Conservation Biology and National Research Center for Wildlife-borne Diseases, Institute of Zoology, Chinese Academy of Sciences Beijing, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Li
authors.affiliation: Key Lab of Animal Ecology and Conservation Biology and National Research Center for Wildlife-borne Diseases, Institute of Zoology, Chinese Academy of Sciences Beijing, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Su
authors.affiliation: Key Lab of Animal Ecology and Conservation Biology and National Research Center for Wildlife-borne Diseases, Institute of Zoology, Chinese Academy of Sciences Beijing, China.
authors.forename: Na
authors.initials: N
authors.lastname: Zhao
authors.affiliation: Department of Infectious Diseases, Zhejiang Center for Disease Control and Prevention Hangzhou, China.
authors.forename: Shelan
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Infectious Diseases, Hangzhou Center for Disease Control and Prevention Hangzhou, China.
authors.forename: Li
authors.initials: L
authors.lastname: Xie
authors.affiliation: Beijing Animal Husbandry Station Beijing, China.
authors.forename: Yaxiong
authors.initials: Y
authors.lastname: Jia
authors.affiliation: Department of Infectious Diseases, Hangzhou Center for Disease Control and Prevention Hangzhou, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Ding
authors.affiliation: Institute for Genomics, Biocomputing and Biotechnology, Mississippi State University Mississippi, MS, USA.
authors.forename: Xiufeng
authors.initials: X
authors.lastname: Wan
authors.affiliation: Key Lab of Animal Ecology and Conservation Biology and National Research Center for Wildlife-borne Diseases, Institute of Zoology, Chinese Academy of Sciences Beijing, China.
authors.forename: Hongxuan
authors.initials: H
authors.lastname: He
mesh_terms: D000072283:A549 Cells; D000818:Animals; D002460:Cell Line; D002642:Chick Embryo; D004285:Dogs; D015536:Down-Regulation; D057809:HEK293 Cells; D006388:Hemagglutinins; D054884:Host-Pathogen Interactions / Q000502:physiology; D006801:Humans; D009980:Influenza A virus / Q000472:pathogenicity*; D048369:MAP Kinase Kinase 1 / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000502:physiology*; D061985:Madin Darby Canine Kidney Cells; D010766:Phosphorylation / Q000502:physiology*; D011499:Protein Processing, Post-Translational; D025842:SUMO-1 Protein; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism*; D058207:Sumoylation / Q000502:physiology*; D053719:Tandem Mass Spectrometry; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism; D000098843:Ubiquitin-Conjugating Enzyme UBC9
chemical_list: D006388:Hemagglutinins; D025842:SUMO-1 Protein; C495501:SUMO1 protein, human; D025841:Small Ubiquitin-Related Modifier Proteins; D044763:Ubiquitin-Conjugating Enzymes; D048369:MAP Kinase Kinase 1; D000098843:Ubiquitin-Conjugating Enzyme UBC9
keywords: MEK1; SUMOylation; hemagglutinin; influenza A virus; switch