The initial step in human immunodeficiency virus type 1 GagProPol processing can be regulated by reversible oxidation.

<h4>Background</h4>Maturation of human immunodeficiency virus type 1 (HIV-1) occurs upon activation of HIV-1 protease embedded within GagProPol precursors and cleavage of Gag and GagProPol polyproteins. Although reversible oxidation can regulate mature protease activity as well as retrov...

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Autores principales:	Sarah I Daniels, David A Davis, Erin E Soule, Stephen J Stahl, Irene R Tebbs, Paul Wingfield, Robert Yarchoan
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c8c0085558be4a4ab9875329f5ff1a93
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spelling	oai:doaj.org-article:c8c0085558be4a4ab9875329f5ff1a932021-11-18T07:02:58ZThe initial step in human immunodeficiency virus type 1 GagProPol processing can be regulated by reversible oxidation.1932-620310.1371/journal.pone.0013595https://doaj.org/article/c8c0085558be4a4ab9875329f5ff1a932010-10-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21042582/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Maturation of human immunodeficiency virus type 1 (HIV-1) occurs upon activation of HIV-1 protease embedded within GagProPol precursors and cleavage of Gag and GagProPol polyproteins. Although reversible oxidation can regulate mature protease activity as well as retrovirus maturation, it is possible that the effects of oxidation on viral maturation are mediated in whole, or part, through effects on the initial intramolecular cleavage event of GagProPol. In order assess the effect of reversible oxidation on this event, we developed a system to isolate the first step in protease activation involving GagProPol.<h4>Methodology/principal findings</h4>To determine if oxidation influences this step, we created a GagProPol plasmid construct (pGPfs-1C) that encoded mutations at all cleavage sites except p2/NC, the initial cleavage site in GagProPol. pGPfs-1C was used in an in vitro translation assay to observe the behavior of this initial step without interference from subsequent processing events. Diamide, a sulfhydral oxidizing agent, inhibited processing at p2/NC by >60% for pGPfs-1C and was readily reversed with the reductant, dithiothreitol. The ability to regulate processing by reversible oxidation was lost when the cysteines of the embedded protease were mutated to alanine. Unlike mature protease, which requires only oxidation of cys95 for inhibition, both cysteines of the embedded protease contributed to this inhibition.<h4>Conclusions/significance</h4>We developed a system that can be used to study the first step in the cascade of HIV-1 GagProPol processing and show that reversible oxidation of cysteines of HIV-1 protease embedded in GagProPol can block this initial GagProPol autoprocessing. This type of regulation may be broadly applied to the majority of retroviruses.Sarah I DanielsDavid A DavisErin E SouleStephen J StahlIrene R TebbsPaul WingfieldRobert YarchoanPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 10, p e13595 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sarah I Daniels David A Davis Erin E Soule Stephen J Stahl Irene R Tebbs Paul Wingfield Robert Yarchoan The initial step in human immunodeficiency virus type 1 GagProPol processing can be regulated by reversible oxidation.
description	<h4>Background</h4>Maturation of human immunodeficiency virus type 1 (HIV-1) occurs upon activation of HIV-1 protease embedded within GagProPol precursors and cleavage of Gag and GagProPol polyproteins. Although reversible oxidation can regulate mature protease activity as well as retrovirus maturation, it is possible that the effects of oxidation on viral maturation are mediated in whole, or part, through effects on the initial intramolecular cleavage event of GagProPol. In order assess the effect of reversible oxidation on this event, we developed a system to isolate the first step in protease activation involving GagProPol.<h4>Methodology/principal findings</h4>To determine if oxidation influences this step, we created a GagProPol plasmid construct (pGPfs-1C) that encoded mutations at all cleavage sites except p2/NC, the initial cleavage site in GagProPol. pGPfs-1C was used in an in vitro translation assay to observe the behavior of this initial step without interference from subsequent processing events. Diamide, a sulfhydral oxidizing agent, inhibited processing at p2/NC by >60% for pGPfs-1C and was readily reversed with the reductant, dithiothreitol. The ability to regulate processing by reversible oxidation was lost when the cysteines of the embedded protease were mutated to alanine. Unlike mature protease, which requires only oxidation of cys95 for inhibition, both cysteines of the embedded protease contributed to this inhibition.<h4>Conclusions/significance</h4>We developed a system that can be used to study the first step in the cascade of HIV-1 GagProPol processing and show that reversible oxidation of cysteines of HIV-1 protease embedded in GagProPol can block this initial GagProPol autoprocessing. This type of regulation may be broadly applied to the majority of retroviruses.
format	article
author	Sarah I Daniels David A Davis Erin E Soule Stephen J Stahl Irene R Tebbs Paul Wingfield Robert Yarchoan
author_facet	Sarah I Daniels David A Davis Erin E Soule Stephen J Stahl Irene R Tebbs Paul Wingfield Robert Yarchoan
author_sort	Sarah I Daniels
title	The initial step in human immunodeficiency virus type 1 GagProPol processing can be regulated by reversible oxidation.
title_short	The initial step in human immunodeficiency virus type 1 GagProPol processing can be regulated by reversible oxidation.
title_full	The initial step in human immunodeficiency virus type 1 GagProPol processing can be regulated by reversible oxidation.
title_fullStr	The initial step in human immunodeficiency virus type 1 GagProPol processing can be regulated by reversible oxidation.
title_full_unstemmed	The initial step in human immunodeficiency virus type 1 GagProPol processing can be regulated by reversible oxidation.
title_sort	initial step in human immunodeficiency virus type 1 gagpropol processing can be regulated by reversible oxidation.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/c8c0085558be4a4ab9875329f5ff1a93
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The initial step in human immunodeficiency virus type 1 GagProPol processing can be regulated by reversible oxidation.

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