title: HIV-1 antagonism of CD317 is species specific and involves Vpu-mediated proteasomal degradation of the restriction factor.
abstract: Mammals encode proteins that inhibit viral replication at the cellular level. In turn, certain viruses have evolved genes that can functionally counteract these intrinsic restrictions. Human CD317 (BST-2/HM1.24/tetherin) is a restriction factor that blocks release of human immunodeficiency virus type 1 (HIV-1) from the cell surface and can be overcome by HIV-1 Vpu. Here, we show that mouse and rat CD317 potently inhibit HIV-1 release but are resistant to Vpu. Interspecies chimeras reveal that the rodent-specific resistance and human-specific sensitivity to Vpu antagonism involve all three major structural domains of CD317. To promote virus release, Vpu depletes cellular pools of human CD317, but not of the rodent orthologs, by accelerating its degradation via the 20S proteasome. Thus, HIV-1 Vpu suppresses the expression of the CD317 antiviral factor in human cells, and the species-specific resistance to this suppression may guide the development of small animal models of HIV infection.
authors.affiliation: Department of Virology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Goffinet
authors.forename: Ina
authors.initials: I
authors.lastname: Allespach
authors.forename: Stefanie
authors.initials: S
authors.lastname: Homann
authors.forename: Hanna-Mari
authors.initials: HM
authors.lastname: Tervo
authors.forename: Anja
authors.initials: A
authors.lastname: Habermann
authors.forename: Daniel
authors.initials: D
authors.lastname: Rupp
authors.forename: Lena
authors.initials: L
authors.lastname: Oberbremer
authors.forename: Christian
authors.initials: C
authors.lastname: Kern
authors.forename: Nadine
authors.initials: N
authors.lastname: Tibroni
authors.forename: Sonja
authors.initials: S
authors.lastname: Welsch
authors.forename: Jacomine
authors.initials: J
authors.lastname: Krijnse-Locker
authors.forename: George
authors.initials: G
authors.lastname: Banting
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Kräusslich
authors.forename: Oliver T
authors.initials: OT
authors.lastname: Fackler
authors.forename: Oliver T
authors.initials: OT
authors.lastname: Keppler
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D058851:GPI-Linked Proteins; D015497:HIV-1 / Q000276:immunology* / Q000472:pathogenicity*; D054298:Human Immunodeficiency Virus Proteins / Q000502:physiology*; D006801:Humans; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors* / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D051381:Rats; D054334:Viral Regulatory and Accessory Proteins / Q000502:physiology*; D037521:Virulence Factors / Q000502:physiology*; D000074010:Bone Marrow Stromal Antigen 2; D000086082:Viroporin Proteins
chemical_list: D015703:Antigens, CD; D058851:GPI-Linked Proteins; D054298:Human Immunodeficiency Virus Proteins; D008562:Membrane Glycoproteins; D054334:Viral Regulatory and Accessory Proteins; D037521:Virulence Factors; C094572:BST2 protein, human; D000074010:Bone Marrow Stromal Antigen 2; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins