tetherin restricts productive hiv-1 cell-to-cell transmissiontetherin限制生产hiv - 1细胞间传播.pdfVIP

Tetherin Restricts Productive HIV-1 Cell-to-Cell Transmission 1. 1. 1 1 Nicoletta Casartelli , Marion Sourisseau , Jerome Feldmann , Florence Guivel-Benhassine , Adeline 2 ` 3 4 1 Mallet , Anne-Genevieve Marcelin , John Guatelli , Olivier Schwartz * 1 Institut Pasteur, Virus and Immunity Unit, URA CNRS 3015, Paris, France, 2 Plateforme de Microscopie Electronique, Institut Pasteur, Paris, France, 3 UPMC University Paris ˆ ´ ˆ ` 06, and Laboratoire de Virologie, Hopital Pitie-Salpetriere, Paris, France, 4 Department of Medicine, University of California San Diego, La Jolla, California, United States of America Abstract 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 DVpu HIV, were used as donor cells and cocultivated with target lymphocytes. We show that tetherin inhibits productive cell-to-cell transmission of DVpu 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 trans