title: The epidermal growth factor receptor regulates cofilin activity and promotes transmissible gastroenteritis virus entry into intestinal epithelial cells.
abstract: Transmissible gastroenteritis virus (TGEV), a coronavirus, causes severe diarrhea and high mortality in newborn piglets. The porcine intestinal epithelium is the target of TGEV infection, but the mechanisms that TGEV disrupts the actin cytoskeleton and invades the host epithelium remain largely unknown. We not only found that TGEV infection stimulates F-actin to gather at the cell membrane but the disruption of F-actin inhibits TGEV entry as well. Cofilin is involved in F-actin reorganization and TGEV entry. The TGEV spike protein is capable of binding with EGFR, activating the downstream phosphoinositide-3 kinase (PI3K), then causing the phosphorylation of cofilin and F-actin polymerization via Rac1/Cdc42 GTPases. Inhibition of EGFR and PI3K decreases the entry of TGEV. EGFR is also the upstream activator of mitogen-activated protein kinase (MAPK) signaling pathways that is involved in F-actin reorganization. Additionally, lipid rafts act as signal platforms for the EGFR-associated signaling cascade and correlate with the adhesion of TGEV. In conlusion, these results provide valuable data of the mechanisms which are responsible for the TGEV pathogenesis and may lead to the development of new methods about controlling TGEV.
authors.affiliation: Veterinary College, Nanjing Agricultural University, Nanjing, Jiangsu, PR China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Hu
authors.affiliation: Veterinary College, Nanjing Agricultural University, Nanjing, Jiangsu, PR China.
authors.forename: Liqi
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Veterinary College, Nanjing Agricultural University, Nanjing, Jiangsu, PR China.
authors.forename: Xing
authors.initials: X
authors.lastname: Yang
authors.affiliation: Life Science College, Nanjing Agricultural University, Nanjing, Jiangsu, PR China.
authors.forename: Jian
authors.initials: J
authors.lastname: Lin
authors.affiliation: Veterinary College, Nanjing Agricultural University, Nanjing, Jiangsu, PR China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Yang
mesh_terms: D000818:Animals; D002460:Cell Line; D051338:Cofilin 1 / Q000276:immunology*; D004847:Epithelial Cells / Q000276:immunology / Q000821:virology*; D066246:ErbB Receptors / Q000276:immunology*; D005761:Gastroenteritis, Transmissible, of Swine / Q000821:virology; D057809:HEK293 Cells; D006801:Humans; D007422:Intestines / Q000166:cytology / Q000276:immunology / Q000821:virology*; D021962:Membrane Microdomains; D013552:Swine; D005760:Transmissible gastroenteritis virus / Q000502:physiology*; D053586:Virus Internalization
chemical_list: D051338:Cofilin 1; D066246:ErbB Receptors
keywords: EGFR; F-actin; Immune response; Immunity; Immunology and Microbiology Section; TGEV; cofilin