title: Phosphatidylinositol 4-kinase IIIβ is required for severe acute respiratory syndrome coronavirus spike-mediated cell entry.
abstract: Phosphatidylinositol kinases (PI kinases) play an important role in the life cycle of several viruses after infection. Using gene knockdown technology, we demonstrate that phosphatidylinositol 4-kinase IIIβ (PI4KB) is required for cellular entry by pseudoviruses bearing the severe acute respiratory syndrome-coronavirus (SARS-CoV) spike protein and that the cell entry mediated by SARS-CoV spike protein is strongly inhibited by knockdown of PI4KB. Consistent with this observation, pharmacological inhibitors of PI4KB blocked entry of SARS pseudovirions. Further research suggested that PI4P plays an essential role in SARS-CoV spike-mediated entry, which is regulated by the PI4P lipid microenvironment. We further demonstrate that PI4KB does not affect virus entry at the SARS-CoV S-ACE2 binding interface or at the stage of virus internalization but rather at or before virus fusion. Taken together, these results indicate a new function for PI4KB and suggest a new drug target for preventing SARS-CoV infection.
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Peking Union Medical College, Tsinghua University, Chinese Academy of Medical Sciences, Beijing 100005, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Yang
authors.forename: Ping
authors.initials: P
authors.lastname: Ma
authors.forename: Jianshe
authors.initials: J
authors.lastname: Lang
authors.forename: Yanli
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jiejie
authors.initials: J
authors.lastname: Deng
authors.forename: Xiangwu
authors.initials: X
authors.lastname: Ju
authors.forename: Gongyi
authors.initials: G
authors.lastname: Zhang
authors.forename: Chengyu
authors.initials: C
authors.lastname: Jiang
mesh_terms: D000818:Animals; D002522:Chlorocebus aethiops; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D057809:HEK293 Cells; D006801:Humans; D008563:Membrane Lipids / Q000378:metabolism; D015778:Minor Histocompatibility Antigens; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors / Q000378:metabolism*; D045473:Severe acute respiratory syndrome-related coronavirus / Q000378:metabolism*; D045169:Severe Acute Respiratory Syndrome / Q000188:drug therapy / Q000378:metabolism*; D014771:Virion / Q000378:metabolism*; D053586:Virus Internalization
chemical_list: D004791:Enzyme Inhibitors; D008563:Membrane Lipids; D015778:Minor Histocompatibility Antigens; D017853:Phosphotransferases (Alcohol Group Acceptor); C402182:phosphatidylinositol phosphate 4-kinase