Tetherin restricts productive HIV-1 cell-to-cell transmission.
The IFN-inducible antiviral protein tetherin (or BST-2/CD317/HM1.24) impairs release of mature HIV-1 particles from infected cells. HIV-1 Vpu antagonizes the effect of tetherin. The fate of virions trapped at the cell surface remains poorly understood. Here, we asked whether tetherin impairs HIV cell-to-cell transmission, a major means of viral spread. Tetherin-positive or -negative cells, infected with wild-type or DeltaVpu HIV, were used as donor cells and cocultivated with target lymphocytes. We show that tetherin inhibits productive cell-to-cell transmission of DeltaVpu to targets and impairs that of WT HIV. Tetherin accumulates with Gag at the contact zone between infected and target cells, but does not prevent the formation of virological synapses. In the presence of tetherin, viruses are then mostly transferred to targets as abnormally large patches. These viral aggregates do not efficiently promote infection after transfer, because they accumulate at the surface of target cells and are impaired in their fusion capacities. Tetherin, by imprinting virions in donor cells, is the first example of a surface restriction factor limiting viral cell-to-cell spread.
Casartelli
Nicoletta
N
Institut Pasteur, Virus and Immunity Unit, URA CNRS 3015, Paris, France.
Sourisseau
Marion
M
Feldmann
Jerome
J
Guivel-Benhassine
Florence
F
Mallet
Adeline
A
Marcelin
Anne-Geneviève
AG
Guatelli
John
J
Schwartz
Olivier
O
D015703:Antigens, CD / Q000378:metabolism*; D015153:Blotting, Western; D002450:Cell Communication; D002459:Cell Fusion; D002478:Cells, Cultured; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D058851:GPI-Linked Proteins; D015683:Gene Products, gag / Q000235:genetics / Q000378:metabolism; D015658:HIV Infections / Q000378:metabolism* / Q000517:prevention & control / Q000635:transmission*; D015497:HIV-1 / Q000254:growth & development*; D054298:Human Immunodeficiency Virus Proteins / Q000378:metabolism; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism*; D013601:T-Lymphocytes; D054334:Viral Regulatory and Accessory Proteins / Q000378:metabolism; D014771:Virion / Q000378:metabolism*; D014779:Virus Replication; D000074010:Bone Marrow Stromal Antigen 2; D000086082:Viroporin Proteins
D015703:Antigens, CD; D058851:GPI-Linked Proteins; D015683:Gene Products, gag; D054298:Human Immunodeficiency Virus Proteins; D008562:Membrane Glycoproteins; D054334:Viral Regulatory and Accessory Proteins; C094572:BST2 protein, human; D000074010:Bone Marrow Stromal Antigen 2; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins