HIV-1 Gag Blocks Selenite-Induced Stress Granule Assembly by Altering the mRNA Cap-Binding Complex

ABSTRACT Stress granules (SGs) are dynamic accumulations of stalled preinitiation complexes and translational machinery that assemble under stressful conditions. Sodium selenite (Se) induces the assembly of noncanonical type II SGs that differ in morphology, composition, and mechanism of assembly fr...

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Autores principales:	Alessandro Cinti, Valerie Le Sage, Marwan Ghanem, Andrew J. Mouland
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2016
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/c48e5d0f17fd46528268b3c987349f73
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spelling	oai:doaj.org-article:c48e5d0f17fd46528268b3c987349f732021-11-15T15:41:41ZHIV-1 Gag Blocks Selenite-Induced Stress Granule Assembly by Altering the mRNA Cap-Binding Complex10.1128/mBio.00329-162150-7511https://doaj.org/article/c48e5d0f17fd46528268b3c987349f732016-05-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00329-16https://doaj.org/toc/2150-7511ABSTRACT Stress granules (SGs) are dynamic accumulations of stalled preinitiation complexes and translational machinery that assemble under stressful conditions. Sodium selenite (Se) induces the assembly of noncanonical type II SGs that differ in morphology, composition, and mechanism of assembly from canonical SGs. Se inhibits translation initiation by altering the cap-binding activity of eukaryotic translation initiation factor 4E (eIF4E)-binding protein 1 (4EBP1). In this work, we show that human immunodeficiency virus type 1 (HIV-1) Gag is able to block the assembly of type II noncanonical SGs to facilitate continued Gag protein synthesis. We demonstrate that expression of Gag reduces the amount of hypophosphorylated 4EBP1 associated with the 5′ cap potentially through an interaction with its target, eIF4E. These results suggest that the assembly of SGs is an important host antiviral defense that HIV-1 has evolved for inhibition through several distinct mechanisms. IMPORTANCE The antiviral stress response is an important host defense that many viruses, including HIV-1, have evolved to evade. Selenite induces a block in translation and leads to stress granule assembly through the sequestration of eIF4E by binding hypophosphorylated 4EBP1. In this work, we demonstrate that in the face of selenite-induced stress, HIV-1 is able to maintain Gag mRNA translation and to elicit a blockade to selenite-induced stress granule assembly by altering the amount of hypophosphorylated 4EBP1 on the 5′ cap.Alessandro CintiValerie Le SageMarwan GhanemAndrew J. MoulandAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 7, Iss 2 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Alessandro Cinti Valerie Le Sage Marwan Ghanem Andrew J. Mouland HIV-1 Gag Blocks Selenite-Induced Stress Granule Assembly by Altering the mRNA Cap-Binding Complex
description	ABSTRACT Stress granules (SGs) are dynamic accumulations of stalled preinitiation complexes and translational machinery that assemble under stressful conditions. Sodium selenite (Se) induces the assembly of noncanonical type II SGs that differ in morphology, composition, and mechanism of assembly from canonical SGs. Se inhibits translation initiation by altering the cap-binding activity of eukaryotic translation initiation factor 4E (eIF4E)-binding protein 1 (4EBP1). In this work, we show that human immunodeficiency virus type 1 (HIV-1) Gag is able to block the assembly of type II noncanonical SGs to facilitate continued Gag protein synthesis. We demonstrate that expression of Gag reduces the amount of hypophosphorylated 4EBP1 associated with the 5′ cap potentially through an interaction with its target, eIF4E. These results suggest that the assembly of SGs is an important host antiviral defense that HIV-1 has evolved for inhibition through several distinct mechanisms. IMPORTANCE The antiviral stress response is an important host defense that many viruses, including HIV-1, have evolved to evade. Selenite induces a block in translation and leads to stress granule assembly through the sequestration of eIF4E by binding hypophosphorylated 4EBP1. In this work, we demonstrate that in the face of selenite-induced stress, HIV-1 is able to maintain Gag mRNA translation and to elicit a blockade to selenite-induced stress granule assembly by altering the amount of hypophosphorylated 4EBP1 on the 5′ cap.
format	article
author	Alessandro Cinti Valerie Le Sage Marwan Ghanem Andrew J. Mouland
author_facet	Alessandro Cinti Valerie Le Sage Marwan Ghanem Andrew J. Mouland
author_sort	Alessandro Cinti
title	HIV-1 Gag Blocks Selenite-Induced Stress Granule Assembly by Altering the mRNA Cap-Binding Complex
title_short	HIV-1 Gag Blocks Selenite-Induced Stress Granule Assembly by Altering the mRNA Cap-Binding Complex
title_full	HIV-1 Gag Blocks Selenite-Induced Stress Granule Assembly by Altering the mRNA Cap-Binding Complex
title_fullStr	HIV-1 Gag Blocks Selenite-Induced Stress Granule Assembly by Altering the mRNA Cap-Binding Complex
title_full_unstemmed	HIV-1 Gag Blocks Selenite-Induced Stress Granule Assembly by Altering the mRNA Cap-Binding Complex
title_sort	hiv-1 gag blocks selenite-induced stress granule assembly by altering the mrna cap-binding complex
publisher	American Society for Microbiology
publishDate	2016
url	https://doaj.org/article/c48e5d0f17fd46528268b3c987349f73
work_keys_str_mv	AT alessandrocinti hiv1gagblocksseleniteinducedstressgranuleassemblybyalteringthemrnacapbindingcomplex AT valerielesage hiv1gagblocksseleniteinducedstressgranuleassemblybyalteringthemrnacapbindingcomplex AT marwanghanem hiv1gagblocksseleniteinducedstressgranuleassemblybyalteringthemrnacapbindingcomplex AT andrewjmouland hiv1gagblocksseleniteinducedstressgranuleassemblybyalteringthemrnacapbindingcomplex
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HIV-1 Gag Blocks Selenite-Induced Stress Granule Assembly by Altering the mRNA Cap-Binding Complex

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