title: BST-2 restricts IAV release and is countered by the viral M2 protein.
abstract: BST-2 (tetherin, CD317, and HM1.24) is induced by interferon and restricts virus release by tethering the enveloped viruses to the cell surface. The effect of BST-2 on influenza A virus (IAV) infection has been inconclusive. In the present study, we report that BST-2 diminishes the production of IAV virus-like particles (VLPs) that are generated by viral neuraminidase and hemagglutinin proteins to a much greater degree than it inhibits the production of wild-type IAV particles. This relatively weaker inhibition of IAV is associated with reduction in BST-2 levels, which is caused by the M2 protein that interacts with BST-2 and leads to down-regulation of cell surface BST-2 via the proteasomal pathway. Similarly to the viral antagonist Vpu, M2 also rescues the production of human immunodeficiency virus-1 VLPs and IAV VLPs in the presence of BST-2. Replication of wild-type and the M2-deleted viruses were both inhibited by BST-2, with the M2-deleted IAV being more restricted. These data reveal one mechanism that IAV employs to counter restriction by BST-2.
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, and Center for AIDS Research, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, PR China.
authors.forename: Siqi
authors.initials: S
authors.lastname: Hu
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, and Center for AIDS Research, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, PR China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Yin
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, and Center for AIDS Research, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, PR China.
authors.forename: Shan
authors.initials: S
authors.lastname: Mei
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, and Center for AIDS Research, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, PR China.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, and Center for AIDS Research, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, PR China.
authors.forename: Fengwen
authors.initials: F
authors.lastname: Xu
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, and Center for AIDS Research, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, PR China.
authors.forename: Hong
authors.initials: H
authors.lastname: Sun
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, and Center for AIDS Research, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, PR China.
authors.forename: Xiaoman
authors.initials: X
authors.lastname: Liu
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, PR China.
authors.forename: Shan
authors.initials: S
authors.lastname: Cen
authors.affiliation: McGill University AIDS Centre, Lady Davis Institute, Jewish General Hospital, Montreal H3T 1E2, Canada.
authors.forename: Chen
authors.initials: C
authors.lastname: Liang
authors.affiliation: Institute of Microcirculation, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, PR China lialwork@imc.pumc.edu.cn guofei@ipb.pumc.edu.cn.
authors.forename: Ailing
authors.initials: A
authors.lastname: Li
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, and Center for AIDS Research, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, PR China lialwork@imc.pumc.edu.cn guofei@ipb.pumc.edu.cn.
authors.forename: Fei
authors.initials: F
authors.lastname: Guo
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism; D002522:Chlorocebus aethiops; D004285:Dogs; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D015497:HIV-1 / Q000235:genetics* / Q000378:metabolism; D006367:HeLa Cells; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics* / Q000378:metabolism; D061985:Madin Darby Canine Kidney Cells; D009439:Neuraminidase / Q000235:genetics / Q000378:metabolism; D010957:Plasmids / Q000737:chemistry / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection; D014709:Vero Cells; D014763:Viral Matrix Proteins / Q000235:genetics* / Q000378:metabolism; D014771:Virion / Q000235:genetics / Q000378:metabolism; D057074:Virus Release / Q000235:genetics; D000074010:Bone Marrow Stromal Antigen 2; D000086082:Viroporin Proteins
chemical_list: D015703:Antigens, CD; D058851:GPI-Linked Proteins; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D009439:Neuraminidase; D046988:Proteasome Endopeptidase Complex; D011994:Recombinant Proteins; D014763:Viral Matrix Proteins; C094572:BST2 protein, human; D000074010:Bone Marrow Stromal Antigen 2; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins; C483468:hemagglutinin, human influenza A virus
keywords: BST-2; M2; host restriction factors; influenza virus; innate immunity