title: Feline tetherin is characterized by a short N-terminal region and is counteracted by the feline immunodeficiency virus envelope glycoprotein.
abstract: Tetherin (BST2) is the host cell factor that blocks the particle release of some enveloped viruses. Two putative feline tetherin proteins differing at the level of the N-terminal coding region have recently been described and tested for their antiviral activity. By cloning and comparing the two reported feline tetherins (called here cBST2(504) and cBST2*) and generating specific derivative mutants, this study provides evidence that feline tetherin has a shorter intracytoplasmic domain than those of other known homologues. The minimal tetherin promoter was identified and assayed for its ability to drive tetherin expression in an alpha interferon-inducible manner. We also demonstrated that cBST2(504) is able to dimerize, is localized at the cellular membrane, and impairs human immunodeficiency virus type 1 (HIV-1) particle release, regardless of the presence of the Vpu antagonist accessory protein. While cBST2(504) failed to restrict wild-type feline immunodeficiency virus (FIV) egress, FIV mutants, bearing a frameshift at the level of the envelope-encoding region, were potently blocked. The transient expression of the FIV envelope glycoprotein was able to rescue mutant particle release from feline tetherin-positive cells but did not antagonize human BST2 activity. Moreover, cBST2(504) was capable of specifically immunoprecipitating the FIV envelope glycoprotein. Finally, cBST2(504) also exerted its function on HIV-2 ROD10 and on the simian immunodeficiency virus SIVmac239. Taken together, these results show that feline tetherin does indeed have a short N-terminal region and that the FIV envelope glycoprotein is the predominant factor counteracting tetherin restriction.
authors.affiliation: Department of Molecular Medicine, University of Padua, Padua, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Celestino
authors.forename: Arianna
authors.initials: A
authors.lastname: Calistri
authors.forename: Claudia
authors.initials: C
authors.lastname: Del Vecchio
authors.forename: Cristiano
authors.initials: C
authors.lastname: Salata
authors.forename: Flavia
authors.initials: F
authors.lastname: Chiuppesi
authors.forename: Mauro
authors.initials: M
authors.lastname: Pistello
authors.forename: Alessandra
authors.initials: A
authors.lastname: Borsetti
authors.forename: Giorgio
authors.initials: G
authors.lastname: Palù
authors.forename: Cristina
authors.initials: C
authors.lastname: Parolin
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D002415:Cats / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D016181:Feline Acquired Immunodeficiency Syndrome / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D058851:GPI-Linked Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D016089:Immunodeficiency Virus, Feline / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D016415:Sequence Alignment; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism*; D057074:Virus Release
chemical_list: D058851:GPI-Linked Proteins; D014759:Viral Envelope Proteins