HIV-1 antagonism of CD317 is species specific and involves Vpu-mediated proteasomal degradation of the restriction factor.
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.
Goffinet
Christine
C
Department of Virology, University of Heidelberg, Heidelberg, Germany.
Allespach
Ina
I
Homann
Stefanie
S
Tervo
Hanna-Mari
HM
Habermann
Anja
A
Rupp
Daniel
D
Oberbremer
Lena
L
Kern
Christian
C
Tibroni
Nadine
N
Welsch
Sonja
S
Krijnse-Locker
Jacomine
J
Banting
George
G
Kräusslich
Hans-Georg
HG
Fackler
Oliver T
OT
Keppler
Oliver T
OT
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
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