MCMV-mediated inhibition of the pro-apoptotic Bak protein is required for optimal in vivo replication.

Successful replication and transmission of large DNA viruses such as the cytomegaloviruses (CMV) family of viruses depends on the ability to interfere with multiple aspects of the host immune response. Apoptosis functions as a host innate defence mechanism against viral infection, and the capacity t...

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Autores principales:	Peter Fleming, Marc Kvansakul, Valentina Voigt, Benjamin T Kile, Ruth M Kluck, David C S Huang, Mariapia A Degli-Esposti, Christopher E Andoniou
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/834c338de3e949948bc22fed22f02779
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spelling	oai:doaj.org-article:834c338de3e949948bc22fed22f027792021-11-18T06:05:59ZMCMV-mediated inhibition of the pro-apoptotic Bak protein is required for optimal in vivo replication.1553-73661553-737410.1371/journal.ppat.1003192https://doaj.org/article/834c338de3e949948bc22fed22f027792013-02-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23468630/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Successful replication and transmission of large DNA viruses such as the cytomegaloviruses (CMV) family of viruses depends on the ability to interfere with multiple aspects of the host immune response. Apoptosis functions as a host innate defence mechanism against viral infection, and the capacity to interfere with this process is essential for the replication of many viruses. The Bcl-2 family of proteins are the principle regulators of apoptosis, with two pro-apoptotic members, Bax and Bak, essential for apoptosis to proceed. The m38.5 protein encoded by murine CMV (MCMV) has been identified as Bax-specific inhibitor of apoptosis. Recently, m41.1, a protein product encoded by the m41 open reading frame (ORF) of MCMV, has been shown to inhibit Bak activity in vitro. Here we show that m41.1 is critical for optimal MCMV replication in vivo. Growth of a m41.1 mutant was attenuated in multiple organs, a defect that was not apparent in Bak(-/-) mice. Thus, m41.1 promotes MCMV replication by inhibiting Bak-dependent apoptosis during in vivo infection. The results show that Bax and Bak mediate non-redundant functions during MCMV infection and that the virus produces distinct inhibitors for each protein to counter the activity of these proteins.Peter FlemingMarc KvansakulValentina VoigtBenjamin T KileRuth M KluckDavid C S HuangMariapia A Degli-EspostiChristopher E AndoniouPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 9, Iss 2, p e1003192 (2013)
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 Peter Fleming Marc Kvansakul Valentina Voigt Benjamin T Kile Ruth M Kluck David C S Huang Mariapia A Degli-Esposti Christopher E Andoniou MCMV-mediated inhibition of the pro-apoptotic Bak protein is required for optimal in vivo replication.
description	Successful replication and transmission of large DNA viruses such as the cytomegaloviruses (CMV) family of viruses depends on the ability to interfere with multiple aspects of the host immune response. Apoptosis functions as a host innate defence mechanism against viral infection, and the capacity to interfere with this process is essential for the replication of many viruses. The Bcl-2 family of proteins are the principle regulators of apoptosis, with two pro-apoptotic members, Bax and Bak, essential for apoptosis to proceed. The m38.5 protein encoded by murine CMV (MCMV) has been identified as Bax-specific inhibitor of apoptosis. Recently, m41.1, a protein product encoded by the m41 open reading frame (ORF) of MCMV, has been shown to inhibit Bak activity in vitro. Here we show that m41.1 is critical for optimal MCMV replication in vivo. Growth of a m41.1 mutant was attenuated in multiple organs, a defect that was not apparent in Bak(-/-) mice. Thus, m41.1 promotes MCMV replication by inhibiting Bak-dependent apoptosis during in vivo infection. The results show that Bax and Bak mediate non-redundant functions during MCMV infection and that the virus produces distinct inhibitors for each protein to counter the activity of these proteins.
format	article
author	Peter Fleming Marc Kvansakul Valentina Voigt Benjamin T Kile Ruth M Kluck David C S Huang Mariapia A Degli-Esposti Christopher E Andoniou
author_facet	Peter Fleming Marc Kvansakul Valentina Voigt Benjamin T Kile Ruth M Kluck David C S Huang Mariapia A Degli-Esposti Christopher E Andoniou
author_sort	Peter Fleming
title	MCMV-mediated inhibition of the pro-apoptotic Bak protein is required for optimal in vivo replication.
title_short	MCMV-mediated inhibition of the pro-apoptotic Bak protein is required for optimal in vivo replication.
title_full	MCMV-mediated inhibition of the pro-apoptotic Bak protein is required for optimal in vivo replication.
title_fullStr	MCMV-mediated inhibition of the pro-apoptotic Bak protein is required for optimal in vivo replication.
title_full_unstemmed	MCMV-mediated inhibition of the pro-apoptotic Bak protein is required for optimal in vivo replication.
title_sort	mcmv-mediated inhibition of the pro-apoptotic bak protein is required for optimal in vivo replication.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/834c338de3e949948bc22fed22f02779
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MCMV-mediated inhibition of the pro-apoptotic Bak protein is required for optimal in vivo replication.

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