Tetherin Can Restrict Cell-Free and Cell-Cell Transmission of HIV from Primary Macrophages to T Cells

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Tetherin is a cellular protein that inhibits (or restricts) a broad range of enveloped viruses, including HIV, by physically “tethering” nascent particles to the plasma membrane of infected cells. CD4+ T cells and macrophages are the main targets of HIV in vivo, and both cell types express Tetherin. Although the mechanisms of Tetherin-mediated restriction in model cell lines and T cells are increasingly well understood, experimental data from macrophages are sparse, and partially contradict observations made in other cell types. Here we investigate the sensitivity of Tetherin expression to interferon, and the subcellular localisation of the restriction factor in primary human macrophages. We find that Tetherin inhibits HIV release by retaining nascent particles in macrophage HIV assembly compartments, and can also restrict the transmission of HIV across intercellular contacts between macrophages and T cells. Finally, we demonstrate that the HIV protein Vpu efficiently counteracts Tetherin in macrophages, and thereby ensures viral propagation. Our results, together with other published data, show that Tetherin can efficiently inhibit viral replication in both major target cell types of HIV, regardless of the mode of transmission. These data support the view that efficient counteraction of Tetherin was a crucial factor for the global spread of HIV.

Vyšlo v časopise: Tetherin Can Restrict Cell-Free and Cell-Cell Transmission of HIV from Primary Macrophages to T Cells. PLoS Pathog 10(7): e32767. doi:10.1371/journal.ppat.1004189
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004189

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