Can the HIV-1 splicing machinery be targeted for drug discovery?

Zodwa Dlamini, Rodney Hull Research, Innovation & Engagements Portfolio, Mangosuthu University of Technology, Durban, South Africa Abstract: HIV-1 is able to express multiple protein types and isoforms from a single 9 kb mRNA transcript. These proteins are also expressed at particular stages...

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Autores principales:	Dlamini Z, Hull R
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	Alternative splicing exonic splicing enhancer exonic specific silencer HIV-1 SR proteins hnRNP Rev Tat Vpr Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/721b7da5553147468d2c4ab2021b8477
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spelling	oai:doaj.org-article:721b7da5553147468d2c4ab2021b84772021-12-02T07:14:32ZCan the HIV-1 splicing machinery be targeted for drug discovery?1179-1373https://doaj.org/article/721b7da5553147468d2c4ab2021b84772017-03-01T00:00:00Zhttps://www.dovepress.com/can-the-hiv-1-splicing-machinery-be-targeted-for-drug-discovery-peer-reviewed-article-HIVhttps://doaj.org/toc/1179-1373Zodwa Dlamini, Rodney Hull Research, Innovation & Engagements Portfolio, Mangosuthu University of Technology, Durban, South Africa Abstract: HIV-1 is able to express multiple protein types and isoforms from a single 9 kb mRNA transcript. These proteins are also expressed at particular stages of viral development, and this is achieved through the control of alternative splicing and the export of these transcripts from the nucleus. The nuclear export is controlled by the HIV protein Rev being required to transport incompletely spliced and partially spliced mRNA from the nucleus where they are normally retained. This implies a close relationship between the control of alternate splicing and the nuclear export of mRNA in the control of HIV-1 viral proliferation. This review discusses both the processes. The specificity and regulation of splicing in HIV-1 is controlled by the use of specific splice sites as well as exonic splicing enhancer and exonic splicing silencer sequences. The use of these silencer and enhancer sequences is dependent on the serine arginine family of proteins as well as the heterogeneous nuclear ribonucleoprotein family of proteins that bind to these sequences and increase or decrease splicing. Since alternative splicing is such a critical factor in viral development, it presents itself as a promising drug target. This review aims to discuss the inhibition of splicing, which would stall viral development, as an anti-HIV therapeutic strategy. In this review, the most recent knowledge of splicing in human immunodeficiency viral development and the latest therapeutic strategies targeting human immunodeficiency viral splicing are discussed. Keywords: alternative splicing, exonic splicing enhancer, exonic specific silencer, splicing based therapies, SR proteins, hnRNP, Rev, Tat, VprDlamini ZHull RDove Medical PressarticleAlternative splicingexonic splicing enhancerexonic specific silencerHIV-1SR proteinshnRNPRevTatVprImmunologic diseases. AllergyRC581-607ENHIV/AIDS: Research and Palliative Care, Vol Volume 9, Pp 63-75 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Alternative splicing exonic splicing enhancer exonic specific silencer HIV-1 SR proteins hnRNP Rev Tat Vpr Immunologic diseases. Allergy RC581-607
spellingShingle	Alternative splicing exonic splicing enhancer exonic specific silencer HIV-1 SR proteins hnRNP Rev Tat Vpr Immunologic diseases. Allergy RC581-607 Dlamini Z Hull R Can the HIV-1 splicing machinery be targeted for drug discovery?
description	Zodwa Dlamini, Rodney Hull Research, Innovation & Engagements Portfolio, Mangosuthu University of Technology, Durban, South Africa Abstract: HIV-1 is able to express multiple protein types and isoforms from a single 9 kb mRNA transcript. These proteins are also expressed at particular stages of viral development, and this is achieved through the control of alternative splicing and the export of these transcripts from the nucleus. The nuclear export is controlled by the HIV protein Rev being required to transport incompletely spliced and partially spliced mRNA from the nucleus where they are normally retained. This implies a close relationship between the control of alternate splicing and the nuclear export of mRNA in the control of HIV-1 viral proliferation. This review discusses both the processes. The specificity and regulation of splicing in HIV-1 is controlled by the use of specific splice sites as well as exonic splicing enhancer and exonic splicing silencer sequences. The use of these silencer and enhancer sequences is dependent on the serine arginine family of proteins as well as the heterogeneous nuclear ribonucleoprotein family of proteins that bind to these sequences and increase or decrease splicing. Since alternative splicing is such a critical factor in viral development, it presents itself as a promising drug target. This review aims to discuss the inhibition of splicing, which would stall viral development, as an anti-HIV therapeutic strategy. In this review, the most recent knowledge of splicing in human immunodeficiency viral development and the latest therapeutic strategies targeting human immunodeficiency viral splicing are discussed. Keywords: alternative splicing, exonic splicing enhancer, exonic specific silencer, splicing based therapies, SR proteins, hnRNP, Rev, Tat, Vpr
format	article
author	Dlamini Z Hull R
author_facet	Dlamini Z Hull R
author_sort	Dlamini Z
title	Can the HIV-1 splicing machinery be targeted for drug discovery?
title_short	Can the HIV-1 splicing machinery be targeted for drug discovery?
title_full	Can the HIV-1 splicing machinery be targeted for drug discovery?
title_fullStr	Can the HIV-1 splicing machinery be targeted for drug discovery?
title_full_unstemmed	Can the HIV-1 splicing machinery be targeted for drug discovery?
title_sort	can the hiv-1 splicing machinery be targeted for drug discovery?
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/721b7da5553147468d2c4ab2021b8477
work_keys_str_mv	AT dlaminiz canthehiv1splicingmachinerybetargetedfordrugdiscovery AT hullr canthehiv1splicingmachinerybetargetedfordrugdiscovery
_version_	1718399520940752896

Can the HIV-1 splicing machinery be targeted for drug discovery?

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