BST2/Tetherin Enhances Entry of Human Cytomegalovirus

Interferon-induced BST2/Tetherin prevents budding of vpu-deficient HIV-1 by tethering mature viral particles to the plasma membrane. BST2 also inhibits release of other enveloped viruses including Ebola virus and Kaposi's sarcoma associated herpesvirus (KSHV), indicating that BST2 is a broadly...

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Main Authors:	Viswanathan, Kasinath, Smith, M. Shane, Malouli, Daniel, Mansouri, Mandana, Nelson, Jay A., Früh, Klaus
Format:	Online
Language:	English
Published:	Public Library of Science 2011
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3207899/

id	pubmed-3207899
recordtype	oai_dc
spelling	pubmed-32078992011-11-09 BST2/Tetherin Enhances Entry of Human Cytomegalovirus Viswanathan, Kasinath Smith, M. Shane Malouli, Daniel Mansouri, Mandana Nelson, Jay A. Früh, Klaus Research Article Interferon-induced BST2/Tetherin prevents budding of vpu-deficient HIV-1 by tethering mature viral particles to the plasma membrane. BST2 also inhibits release of other enveloped viruses including Ebola virus and Kaposi's sarcoma associated herpesvirus (KSHV), indicating that BST2 is a broadly acting antiviral host protein. Unexpectedly however, recovery of human cytomegalovirus (HCMV) from supernatants of BST2-expressing human fibroblasts was increased rather than decreased. Furthermore, BST2 seemed to enhance viral entry into cells since more virion proteins were released into BST2-expressing cells and subsequent viral gene expression was elevated. A significant increase in viral entry was also observed upon induction of endogenous BST2 during differentiation of the pro-monocytic cell line THP-1. Moreover, treatment of primary human monocytes with siRNA to BST2 reduced HCMV infection, suggesting that BST2 facilitates entry of HCMV into cells expressing high levels of BST2 either constitutively or in response to exogenous stimuli. Since BST2 is present in HCMV particles we propose that HCMV entry is enhanced via a reverse-tethering mechanism with BST2 in the viral envelope interacting with BST2 in the target cell membrane. Our data suggest that HCMV not only counteracts the well-established function of BST2 as inhibitor of viral egress but also employs this anti-viral protein to gain entry into BST2-expressing hematopoietic cells, a process that might play a role in hematogenous dissemination of HCMV. Public Library of Science 2011-11-03 /pmc/articles/PMC3207899/ /pubmed/22072961 http://dx.doi.org/10.1371/journal.ppat.1002332 Text en Viswanathan et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Viswanathan, Kasinath Smith, M. Shane Malouli, Daniel Mansouri, Mandana Nelson, Jay A. Früh, Klaus
spellingShingle	Viswanathan, Kasinath Smith, M. Shane Malouli, Daniel Mansouri, Mandana Nelson, Jay A. Früh, Klaus BST2/Tetherin Enhances Entry of Human Cytomegalovirus
author_facet	Viswanathan, Kasinath Smith, M. Shane Malouli, Daniel Mansouri, Mandana Nelson, Jay A. Früh, Klaus
author_sort	Viswanathan, Kasinath
title	BST2/Tetherin Enhances Entry of Human Cytomegalovirus
title_short	BST2/Tetherin Enhances Entry of Human Cytomegalovirus
title_full	BST2/Tetherin Enhances Entry of Human Cytomegalovirus
title_fullStr	BST2/Tetherin Enhances Entry of Human Cytomegalovirus
title_full_unstemmed	BST2/Tetherin Enhances Entry of Human Cytomegalovirus
title_sort	bst2/tetherin enhances entry of human cytomegalovirus
description	Interferon-induced BST2/Tetherin prevents budding of vpu-deficient HIV-1 by tethering mature viral particles to the plasma membrane. BST2 also inhibits release of other enveloped viruses including Ebola virus and Kaposi's sarcoma associated herpesvirus (KSHV), indicating that BST2 is a broadly acting antiviral host protein. Unexpectedly however, recovery of human cytomegalovirus (HCMV) from supernatants of BST2-expressing human fibroblasts was increased rather than decreased. Furthermore, BST2 seemed to enhance viral entry into cells since more virion proteins were released into BST2-expressing cells and subsequent viral gene expression was elevated. A significant increase in viral entry was also observed upon induction of endogenous BST2 during differentiation of the pro-monocytic cell line THP-1. Moreover, treatment of primary human monocytes with siRNA to BST2 reduced HCMV infection, suggesting that BST2 facilitates entry of HCMV into cells expressing high levels of BST2 either constitutively or in response to exogenous stimuli. Since BST2 is present in HCMV particles we propose that HCMV entry is enhanced via a reverse-tethering mechanism with BST2 in the viral envelope interacting with BST2 in the target cell membrane. Our data suggest that HCMV not only counteracts the well-established function of BST2 as inhibitor of viral egress but also employs this anti-viral protein to gain entry into BST2-expressing hematopoietic cells, a process that might play a role in hematogenous dissemination of HCMV.
publisher	Public Library of Science
publishDate	2011
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3207899/
_version_	1611485456653877248

BST2/Tetherin Enhances Entry of Human Cytomegalovirus

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