title: Cloning and characterization of the antiviral activity of feline Tetherin/BST-2.
abstract: Human Tetherin/BST-2 has recently been identified as a cellular antiviral factor that blocks the release of various enveloped viruses. In this study, we cloned a cDNA fragment encoding a feline homolog of Tetherin/BST-2 and characterized the protein product. The degree of amino acid sequence identity between human Tetherin/BST-2 and the feline homolog was 44.4%. Similar to human Tetherin/BST-2, the expression of feline Tetherin/BST-2 mRNA was inducible by type I interferon (IFN). Exogenous expression of feline Tetherin/BST-2 efficiently inhibited the release of feline endogenous retrovirus RD-114. The extracellular domain of feline Tetherin/BST-2 has two putative N-linked glycosylation sites, N79 and N119. Complete loss of N-linked glycosylation by introduction of mutations into both sites resulted in almost complete abolition of its antiviral activity. In addition, feline Tetherin/BST-2 was insensitive to antagonism by HIV-1 Vpu, although the antiviral activity of human Tetherin/BST-2 was antagonized by HIV-1 Vpu. Our data suggest that feline Tetherin/BST-2 functions as a part of IFN-induced innate immunity against virus infection and that the induction of feline Tetherin/BST-2 in vivo may be effective as a novel antiviral strategy for viral infection.
authors.affiliation: Department of Emerging Infectious Diseases, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan.
authors.forename: Aiko
authors.initials: A
authors.lastname: Fukuma
authors.forename: Masumi
authors.initials: M
authors.lastname: Abe
authors.forename: Yuko
authors.initials: Y
authors.lastname: Morikawa
authors.forename: Takayuki
authors.initials: T
authors.lastname: Miyazawa
authors.forename: Jiro
authors.initials: J
authors.lastname: Yasuda
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000998:Antiviral Agents / Q000378:metabolism*; D002415:Cats; D003001:Cloning, Molecular; D020077:Endogenous Retroviruses / Q000187:drug effects / Q000378:metabolism; D006031:Glycosylation / Q000187:drug effects; D057809:HEK293 Cells; D054298:Human Immunodeficiency Virus Proteins / Q000378:metabolism; D006801:Humans; D007372:Interferons / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D008969:Molecular Sequence Data; D020539:Sequence Analysis, Protein; D054334:Viral Regulatory and Accessory Proteins / Q000378:metabolism; D014771:Virion / Q000187:drug effects; D000086082:Viroporin Proteins
chemical_list: D000998:Antiviral Agents; D054298:Human Immunodeficiency Virus Proteins; D007372:Interferons; D008562:Membrane Glycoproteins; D054334:Viral Regulatory and Accessory Proteins; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins