biostudies-literatureIwamoto MJST Core Research for Evolutional Science and TechnologySmoking Research FoundationTakeda Science FoundationJapan Agency for Medical Research and DevelopmentMochida Memorial Foundation for Medical and Pharmaceutical ResearchKyushu University Qdai-jump Research ProgramJapan Science and Technology AgencyYasuda Memorial Medical FoundationJapan Society for the Promotion of Science800-807https://www.ebi.ac.uk/biostudies/studies/S-EPMC6970923biostudies-literatureUnknown295(3)Sodium taurocholate cotransporting polypeptide (NTCP) is expressed at the surface of human hepatocytes and functions as an entry receptor of hepatitis B virus (HBV). Recently, we have reported that epidermal growth factor receptor (EGFR) is involved in NTCP-mediated viral internalization during the cell entry process. Here, we analyzed which function of EGFR is essential for mediating HBV internalization. In contrast to the reported crucial function of EGFR-downstream signaling for the entry of hepatitis C virus (HCV), blockade of EGFR-downstream signaling proteins, including mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K), and signal transducer and activator of transcription (STAT), had no or only minor effects on HBV infection. Instead, deficiency of EGFR endocyThe Journal of biological chemistryThe machinery for endocytosis of epidermal growth factor receptor coordinates the transport of incoming hepatitis B virus to the endosomal network.PMC6970923JP19fk0310114j0003MIRAIJP19J21455JP19fk0310103j0203JP19fk0210036j0002JP19fm0208019j0003JP19fk0310101j1003JP17H04085JP19K16672Suzuki RIwamoto MIwami SOhashi HMatano TAizaki HNishioka KPark SYSureau CSaso WYun JHSugiyama RMuramatsu MOhshima TRyo AWatashi KOhki MWakita TfalseThe machinery for endocytosis of epidermal growth factor receptor coordinates the transport of incoming hepatitis B virus to the endosomal network.Sodium taurocholate cotransporting polypeptide (NTCP) is expressed at the surface of human hepatocytes and functions as an entry receptor of hepatitis B virus (HBV). Recently, we have reported that epidermal growth factor receptor (EGFR) is involved in NTCP-mediated viral internalization during the cell entry process. Here, we analyzed which function of EGFR is essential for mediating HBV internalization. In contrast to the reported crucial function of EGFR-downstream signaling for the entry of hepatitis C virus (HCV), blockade of EGFR-downstream signaling proteins, including mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K), and signal transducer and activator of transcription (STAT), had no or only minor effects on HBV infection. Instead, deficiency of EGFR endocy2020-01-01T00:00:00Z2020 Jan2025-04-26T18:55:41.985Z2021-02-20T22:08:53ZS-EPMC69709233183666310.1074/jbc.AC119.01036610.1074/jbc.ac119.010366