Tetherin Restricts Productive HIV-1 Cell-to-Cell Transmission

PLoS Pathogens

John Guatelli¹  Jerome Feldmann²  Nicoletta Casartelli²  Marion Sourisseau²  Florence Guivel-Benhassine²  Olivier Schwartz²  Adeline Mallet³  Anne-Geneviève Marcelin⁴ 

[1] Department of Medicine, University of California San Diego, La Jolla, California, United States of America;Institut Pasteur, Virus and Immunity Unit, URA CNRS 3015, Paris, France;Plateforme de Microscopie Electronique, Institut Pasteur, Paris, France;UPMC University Paris 06, and Laboratoire de Virologie, Hôpital Pitié-Salpêtrière, Paris, France

关键词: HIV;    Virions;    Cell fusion;    Lymphocytes;    293T cells;    T cells;    HeLa cells;    HIV-1;   

DOI  :  10.1371/journal.ppat.1000955

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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 ΔVpu HIV, were used as donor cells and cocultivated with target lymphocytes. We show that tetherin inhibits productive cell-to-cell transmission of ΔVpu 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.

【 授权许可】

CC BY