Proteasomal degradation of TRIM5alpha during retrovirus restriction.

The host protein TRIM5alpha inhibits retroviral infection at an early post-penetration stage by targeting the incoming viral capsid. While the detailed mechanism of restriction remains unclear, recent studies have implicated the activity of cellular proteasomes in the restriction of retroviral rever...

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Autores principales:	Christopher James Rold, Christopher Aiken
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2008
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/311c936a68f9460e884217fee707e3a9
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spelling	oai:doaj.org-article:311c936a68f9460e884217fee707e3a92021-11-25T05:46:34ZProteasomal degradation of TRIM5alpha during retrovirus restriction.1553-73661553-737410.1371/journal.ppat.1000074https://doaj.org/article/311c936a68f9460e884217fee707e3a92008-05-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18497858/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374The host protein TRIM5alpha inhibits retroviral infection at an early post-penetration stage by targeting the incoming viral capsid. While the detailed mechanism of restriction remains unclear, recent studies have implicated the activity of cellular proteasomes in the restriction of retroviral reverse transcription imposed by TRIM5alpha. Here, we show that TRIM5alpha is rapidly degraded upon encounter of a restriction-susceptible retroviral core. Inoculation of TRIM5alpha-expressing human 293T cells with a saturating level of HIV-1 particles resulted in accelerated degradation of the HIV-1-restrictive rhesus macaque TRIM5alpha protein but not the nonrestrictive human TRIM5alpha protein. Exposure of cells to HIV-1 also destabilized the owl monkey restriction factor TRIMCyp; this was prevented by addition of the inhibitor cyclosporin A and was not observed with an HIV-1 virus containing a mutation in the capsid protein that relieves restriction by TRIMCyp IVHIV. Likewise, human TRIM5alpha was rapidly degraded upon encounter of the restriction-sensitive N-tropic murine leukemia virus (N-MLV) but not the unrestricted B-MLV. Pretreatment of cells with proteasome inhibitors prevented the HIV-1-induced loss of both rhesus macaque TRIM5alpha and TRIMCyp proteins. We also detected degradation of endogenous TRIM5alpha in rhesus macaque cells following HIV-1 infection. We conclude that engagement of a restriction-sensitive retrovirus core results in TRIM5alpha degradation by a proteasome-dependent mechanism.Christopher James RoldChristopher AikenPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 4, Iss 5, p e1000074 (2008)
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 Christopher James Rold Christopher Aiken Proteasomal degradation of TRIM5alpha during retrovirus restriction.
description	The host protein TRIM5alpha inhibits retroviral infection at an early post-penetration stage by targeting the incoming viral capsid. While the detailed mechanism of restriction remains unclear, recent studies have implicated the activity of cellular proteasomes in the restriction of retroviral reverse transcription imposed by TRIM5alpha. Here, we show that TRIM5alpha is rapidly degraded upon encounter of a restriction-susceptible retroviral core. Inoculation of TRIM5alpha-expressing human 293T cells with a saturating level of HIV-1 particles resulted in accelerated degradation of the HIV-1-restrictive rhesus macaque TRIM5alpha protein but not the nonrestrictive human TRIM5alpha protein. Exposure of cells to HIV-1 also destabilized the owl monkey restriction factor TRIMCyp; this was prevented by addition of the inhibitor cyclosporin A and was not observed with an HIV-1 virus containing a mutation in the capsid protein that relieves restriction by TRIMCyp IVHIV. Likewise, human TRIM5alpha was rapidly degraded upon encounter of the restriction-sensitive N-tropic murine leukemia virus (N-MLV) but not the unrestricted B-MLV. Pretreatment of cells with proteasome inhibitors prevented the HIV-1-induced loss of both rhesus macaque TRIM5alpha and TRIMCyp proteins. We also detected degradation of endogenous TRIM5alpha in rhesus macaque cells following HIV-1 infection. We conclude that engagement of a restriction-sensitive retrovirus core results in TRIM5alpha degradation by a proteasome-dependent mechanism.
format	article
author	Christopher James Rold Christopher Aiken
author_facet	Christopher James Rold Christopher Aiken
author_sort	Christopher James Rold
title	Proteasomal degradation of TRIM5alpha during retrovirus restriction.
title_short	Proteasomal degradation of TRIM5alpha during retrovirus restriction.
title_full	Proteasomal degradation of TRIM5alpha during retrovirus restriction.
title_fullStr	Proteasomal degradation of TRIM5alpha during retrovirus restriction.
title_full_unstemmed	Proteasomal degradation of TRIM5alpha during retrovirus restriction.
title_sort	proteasomal degradation of trim5alpha during retrovirus restriction.
publisher	Public Library of Science (PLoS)
publishDate	2008
url	https://doaj.org/article/311c936a68f9460e884217fee707e3a9
work_keys_str_mv	AT christopherjamesrold proteasomaldegradationoftrim5alphaduringretrovirusrestriction AT christopheraiken proteasomaldegradationoftrim5alphaduringretrovirusrestriction
_version_	1718414450560598016

Proteasomal degradation of TRIM5alpha during retrovirus restriction.

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