title: Acid phosphatase 2 (ACP2) is required for membrane fusion during influenza virus entry.
abstract: Influenza viruses exploit host factors to successfully replicate in infected cells. Using small interfering RNA (siRNA) technology, we identified six human genes required for influenza A virus (IAV) replication. Here we focused on the role of acid phosphatase 2 (ACP2), as its knockdown showed the greatest inhibition of IAV replication. In IAV-infected cells, depletion of ACP2 resulted in a significant reduction in the expression of viral proteins and mRNA, and led to the attenuation of virus multi-cycle growth. ACP2 knockdown also decreased replication of seasonal influenza A and B viruses and avian IAVs of the H7 subtype. Interestingly, ACP2 depletion had no effect on the replication of Ebola or hepatitis C virus. Because ACP2 is known to be a lysosomal acid phosphatase, we assessed the role of ACP2 in influenza virus entry. While neither binding of the viral particle to the cell surface nor endosomal acidification was affected in ACP2-depleted cells, fusion of the endosomal and viral membranes was impaired. As a result, downstream steps in viral entry were blocked, including nucleocapsid uncoating and nuclear import of viral ribonucleoproteins. Our results established ACP2 as a necessary host factor for regulating the fusion step of influenza virus entry.
authors.affiliation: Respiratory Viruses Research Laboratory, Discovery Biology Department, Institut Pasteur Korea, Seongnam, Gyeonggi, Republic of Korea.
authors.forename: Jihye
authors.initials: J
authors.lastname: Lee
authors.affiliation: Respiratory Viruses Research Laboratory, Discovery Biology Department, Institut Pasteur Korea, Seongnam, Gyeonggi, Republic of Korea.
authors.forename: Jinhee
authors.initials: J
authors.lastname: Kim
authors.affiliation: Respiratory Viruses Research Laboratory, Discovery Biology Department, Institut Pasteur Korea, Seongnam, Gyeonggi, Republic of Korea.
authors.forename: Kidong
authors.initials: K
authors.lastname: Son
authors.affiliation: Respiratory Viruses Research Laboratory, Discovery Biology Department, Institut Pasteur Korea, Seongnam, Gyeonggi, Republic of Korea.
authors.forename: Anne-Laure Pham Humg
authors.initials: AP
authors.lastname: d'Alexandry d'Orengiani
authors.affiliation: Respiratory Viruses Research Laboratory, Discovery Biology Department, Institut Pasteur Korea, Seongnam, Gyeonggi, Republic of Korea.
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Min
mesh_terms: D000072283:A549 Cells; D000135:Acid Phosphatase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D029563:Cellular Apoptosis Susceptibility Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D004285:Dogs; D011992:Endosomes / Q000378:metabolism; D006801:Humans; D053126:Influenza A Virus, H7N7 Subtype / Q000502:physiology; D009980:Influenza A virus / Q000502:physiology*; D009981:Influenza B virus / Q000502:physiology*; D061985:Madin Darby Canine Kidney Cells; D008856:Microscopy, Fluorescence; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D053586:Virus Internalization; D014779:Virus Replication
chemical_list: D029563:Cellular Apoptosis Susceptibility Protein; D034741:RNA, Small Interfering; C520783:ACP2 protein, human; D000135:Acid Phosphatase