Qian Yang
Nanjing Agricultural University,China
Title: The Epidermal Growth Factor Receptor Regulates Cofilin Activity and Promotes Transmissible Gastroenteritis Virus Entry into Intestinal Epithelial Cells
Biography
Biography: Qian Yang
Abstract
Transmissible gastroenteritis virus (TGEV), a coronavirus, causes severe diarrhea and high mortality in newborn piglets. Porcine intestinal epithelium is the target of TGEV infection, but the mechanisms by which TGEV disrupts the actin cytoskeleton and invades the host epithelium remain largely unknown. In this study, we found that TGEV infection causes F-actin to gather at the cell membrane, and disruption of F-actin inhibits the TGEV entry into IPEC-J2 cells. The actin depolymerizing factor cofilin is critical for actin reorganization and its activity affects TGEV entry. The TGEV spike protein interacts with epidermal growth receptor (EGFR), activating the downstream phosphoinositide-3 kinase (PI3K)-serine/threonine kinase (Akt) signaling pathway, in turn causing the phosphorylation of cofilin and F-actin polymerization via Rac1/Cdc42 GTPases. EGFR is also the upstream regulator of mitogen-activated protein kinase (MAPK) signaling pathways that regulate F-actin. Our research shows that inhibition of EGFR and PI3K inhibits the entry of TGEV and confirms that EGFR is a receptor for TGEV entry. Additionally, lipid rafts act as signal platforms for the EGFR-associated signaling cascade and affect the adhesion of TGEV. Taken together, these results provide valuable insight into the mechanisms responsible for TGEV pathogenesis and may lead to the development of new methods for controlling TGEV
