Study On The Mechanism Of Human Metapneumovirus Activating EGFR To Promote Virus Entry

Objective: Human metapneumovirus is the second largest respiratory pathogen besides human respiratory syncytial virus.The infection rate of children over five years old is as high as 90%.Our group previously found that lipid rafts was involved in human metapneumovirus virus(hMPV)entry,and EGFR is a transmembrane glycoprotein located on membrane lipid rafts,which plays an important role in the infection of a variety of viruses.Therefore,this paper aims to explore the role and related mechanism of epidermal growth factor receptor(EGFR)in human metapneumovirus(hMPV)infection.Methods: The activation levels of EGFR was detected by Western blot after human bronchial epithelial cells(16HBE)were infected with hMPV for certain time.Using EGFR activators and inhibitors to change the expression or activation level of EGFR before infected with hMPV,the activation levels of EGFR and downstream PI3K/AKT signaling pathways were tested by Western blot,and the virus titer was detected by real-time quantitative PCR.Results: The phosphorylation level of EGFR was significantly increased within 5 minutes of hMPV entry,and reached the maximum at 15 min.Activation of EGFR with an activator prior to infection promoted the virus to enter the cell,while inhibition of EGFR reduced viral titer.hMPV activated EGFR early in infection and then initiated PI3K/AKT signaling pathway downstream of EGFR.The cells were pre-treated with EGFR inhibitors and then infected with hMPV,and the activation of PI3K/AKT signaling pathway was significantly inhibited.Conclusion: hMPV infection can activate EGFR and induce the activation of downstream PI3K/AKT signaling pathway,and the activation of EGFR could promote virus entry.