Tetherin can restrict cell-free and cell-cell transmission of HIV from primary macrophages to T cells.

Bst-2/Tetherin inhibits the release of HIV by tethering newly formed virus particles to the plasma membrane of infected cells. Although the mechanisms of Tetherin-mediated restriction are increasingly well understood, the biological relevance of this restriction in the natural target cells of HIV is...

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Autores principales:	Sebastian Giese, Mark Marsh
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/ddc6f9405a9f4d93a5740c49a8efb997
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spelling	oai:doaj.org-article:ddc6f9405a9f4d93a5740c49a8efb9972021-11-25T05:46:19ZTetherin can restrict cell-free and cell-cell transmission of HIV from primary macrophages to T cells.1553-73661553-737410.1371/journal.ppat.1004189https://doaj.org/article/ddc6f9405a9f4d93a5740c49a8efb9972014-07-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24991932/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Bst-2/Tetherin inhibits the release of HIV by tethering newly formed virus particles to the plasma membrane of infected cells. Although the mechanisms of Tetherin-mediated restriction are increasingly well understood, the biological relevance of this restriction in the natural target cells of HIV is unclear. Moreover, whether Tetherin exerts any restriction on the direct cell-cell spread of HIV across intercellular contacts remains controversial. Here we analyse the restriction endogenous Tetherin imposes on HIV transmission from primary human macrophages, one of the main targets of HIV in vivo. We find that the mRNA and protein levels of Tetherin in macrophages are comparable to those in T cells from the same donors, and are highly upregulated by type I interferons. Improved immunocytochemistry protocols enable us to demonstrate that Tetherin localises to the cell surface, the trans-Golgi network, and the macrophage HIV assembly compartments. Tetherin retains budded virions in the assembly compartments, thereby impeding the release and cell-free spread of HIV, but it is not required for the maintenance of these compartments per se. Notably, using a novel assay to quantify cell-cell spread, we show that Tetherin promotes the transfer of virus clusters from macrophages to T cells and thereby restricts the direct transmission of a dual-tropic HIV-1. Kinetic analyses provide support for the notion that this direct macrophage-T cell spread is mediated, at least in part, by so-called virological synapses. Finally, we demonstrate that the viral Vpu protein efficiently downregulates the cell surface and overall levels of Tetherin, and thereby abrogates this HIV restriction in macrophages. Together, our study shows that Tetherin, one of the most potent HIV restriction factors identified to date, can inhibit virus spread from primary macrophages, regardless of the mode of transmission.Sebastian GieseMark MarshPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 10, Iss 7, p e1004189 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Sebastian Giese Mark Marsh Tetherin can restrict cell-free and cell-cell transmission of HIV from primary macrophages to T cells.
description	Bst-2/Tetherin inhibits the release of HIV by tethering newly formed virus particles to the plasma membrane of infected cells. Although the mechanisms of Tetherin-mediated restriction are increasingly well understood, the biological relevance of this restriction in the natural target cells of HIV is unclear. Moreover, whether Tetherin exerts any restriction on the direct cell-cell spread of HIV across intercellular contacts remains controversial. Here we analyse the restriction endogenous Tetherin imposes on HIV transmission from primary human macrophages, one of the main targets of HIV in vivo. We find that the mRNA and protein levels of Tetherin in macrophages are comparable to those in T cells from the same donors, and are highly upregulated by type I interferons. Improved immunocytochemistry protocols enable us to demonstrate that Tetherin localises to the cell surface, the trans-Golgi network, and the macrophage HIV assembly compartments. Tetherin retains budded virions in the assembly compartments, thereby impeding the release and cell-free spread of HIV, but it is not required for the maintenance of these compartments per se. Notably, using a novel assay to quantify cell-cell spread, we show that Tetherin promotes the transfer of virus clusters from macrophages to T cells and thereby restricts the direct transmission of a dual-tropic HIV-1. Kinetic analyses provide support for the notion that this direct macrophage-T cell spread is mediated, at least in part, by so-called virological synapses. Finally, we demonstrate that the viral Vpu protein efficiently downregulates the cell surface and overall levels of Tetherin, and thereby abrogates this HIV restriction in macrophages. Together, our study shows that Tetherin, one of the most potent HIV restriction factors identified to date, can inhibit virus spread from primary macrophages, regardless of the mode of transmission.
format	article
author	Sebastian Giese Mark Marsh
author_facet	Sebastian Giese Mark Marsh
author_sort	Sebastian Giese
title	Tetherin can restrict cell-free and cell-cell transmission of HIV from primary macrophages to T cells.
title_short	Tetherin can restrict cell-free and cell-cell transmission of HIV from primary macrophages to T cells.
title_full	Tetherin can restrict cell-free and cell-cell transmission of HIV from primary macrophages to T cells.
title_fullStr	Tetherin can restrict cell-free and cell-cell transmission of HIV from primary macrophages to T cells.
title_full_unstemmed	Tetherin can restrict cell-free and cell-cell transmission of HIV from primary macrophages to T cells.
title_sort	tetherin can restrict cell-free and cell-cell transmission of hiv from primary macrophages to t cells.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/ddc6f9405a9f4d93a5740c49a8efb997
work_keys_str_mv	AT sebastiangiese tetherincanrestrictcellfreeandcellcelltransmissionofhivfromprimarymacrophagestotcells AT markmarsh tetherincanrestrictcellfreeandcellcelltransmissionofhivfromprimarymacrophagestotcells
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Tetherin can restrict cell-free and cell-cell transmission of HIV from primary macrophages to T cells.

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