Viral reverse transcriptases

Reverse transcriptases (RTs) play a major role in the replication of Retroviridae, Metaviridae, Pseudoviridae, Hepadnaviridae and Caulimoviridae. RTs are enzymes that are able to synthesize DNA using RNA or DNA as templates (DNA polymerase activity), and degrade RNA when forming RNA/DNA hybrids (rib...

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Autores: Menéndez-Arias, Luis, Sebastián-Martín, Alba, Álvarez, Mar
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2016
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/228549
Acceso en línea:http://hdl.handle.net/10261/228549
Access Level:acceso abierto
Palabra clave:Retrovirus
HIV
Hepatitis B virus
DNA polymerase
Antiviral drugs
Ribonuclease H
Fidelity
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spelling Viral reverse transcriptasesMenéndez-Arias, LuisSebastián-Martín, AlbaÁlvarez, MarRetrovirusHIVHepatitis B virusDNA polymeraseAntiviral drugsRibonuclease HFidelityReverse transcriptases (RTs) play a major role in the replication of Retroviridae, Metaviridae, Pseudoviridae, Hepadnaviridae and Caulimoviridae. RTs are enzymes that are able to synthesize DNA using RNA or DNA as templates (DNA polymerase activity), and degrade RNA when forming RNA/DNA hybrids (ribonuclease H activity). In retroviruses and LTR retrotransposons (Metaviridae and Pseudoviridae), the coordinated action of both enzymatic activities converts single-stranded RNA into a double-stranded DNA that is flanked by identical sequences known as long terminal repeats (LTRs). RTs of retroviruses and LTR retrotransposons are active as monomers (e.g. murine leukemia virus RT), homodimers (e.g. Ty3 RT) or heterodimers (e.g. human immunodeficiency virus type 1 (HIV-1) RT). RTs lack proofreading activity and display high intrinsic error rates. Besides, high recombination rates observed in retroviruses are promoted by poor processivity that causes template switching, a hallmark of reverse transcription. HIV-1 RT inhibitors act-ing on its polymerase activity constitute the backbone of current antiretroviral therapies, although novel drugs, including ribonuclease H inhibitors, are still necessary to fight HIV infections. In Hepadnaviridae and Caulimoviridae, reverse transcription leads to the formation of nicked circular DNAs that will be converted into episomal DNA in the host cell nucleus. Structural and biochemical information on their polymerases is limited, although several drugs inhibiting HIV-1 RT are known to be effective against the human hepatitis B virus polymerase. In this review, we summarize current knowledge on reverse tran-scription in the five virus families and discuss available biochemical and structural information on RTs, including their biosynthesis, enzymatic activities, and potential inhibition. © 2016 Elsevier B.V. All rights reservedMinistry of Economyand Competitiveness (BIO2013-48788-C2-1-R) and an institutionalgrant of Fundación Ramón Areces. A. S.-M. is a recipient of a predoctoral fellowship of the Spanish Ministry of Education, Cultureand Sport (grant no. FPU2013-00693)Ministerio de Economía y Competitividad (España)Fundación Ramón ArecesMinisterio de Educación, Cultura y Deporte (España)Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2021202120162021info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/228549reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttp://dx.doi.org/10.1016/j.virusres.2016.12.019Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2285492026-05-22T06:33:51Z
dc.title.none.fl_str_mv Viral reverse transcriptases
title Viral reverse transcriptases
spellingShingle Viral reverse transcriptases
Menéndez-Arias, Luis
Retrovirus
HIV
Hepatitis B virus
DNA polymerase
Antiviral drugs
Ribonuclease H
Fidelity
title_short Viral reverse transcriptases
title_full Viral reverse transcriptases
title_fullStr Viral reverse transcriptases
title_full_unstemmed Viral reverse transcriptases
title_sort Viral reverse transcriptases
dc.creator.none.fl_str_mv Menéndez-Arias, Luis
Sebastián-Martín, Alba
Álvarez, Mar
author Menéndez-Arias, Luis
author_facet Menéndez-Arias, Luis
Sebastián-Martín, Alba
Álvarez, Mar
author_role author
author2 Sebastián-Martín, Alba
Álvarez, Mar
author2_role author
author
dc.contributor.none.fl_str_mv Ministerio de Economía y Competitividad (España)
Fundación Ramón Areces
Ministerio de Educación, Cultura y Deporte (España)
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Retrovirus
HIV
Hepatitis B virus
DNA polymerase
Antiviral drugs
Ribonuclease H
Fidelity
topic Retrovirus
HIV
Hepatitis B virus
DNA polymerase
Antiviral drugs
Ribonuclease H
Fidelity
description Reverse transcriptases (RTs) play a major role in the replication of Retroviridae, Metaviridae, Pseudoviridae, Hepadnaviridae and Caulimoviridae. RTs are enzymes that are able to synthesize DNA using RNA or DNA as templates (DNA polymerase activity), and degrade RNA when forming RNA/DNA hybrids (ribonuclease H activity). In retroviruses and LTR retrotransposons (Metaviridae and Pseudoviridae), the coordinated action of both enzymatic activities converts single-stranded RNA into a double-stranded DNA that is flanked by identical sequences known as long terminal repeats (LTRs). RTs of retroviruses and LTR retrotransposons are active as monomers (e.g. murine leukemia virus RT), homodimers (e.g. Ty3 RT) or heterodimers (e.g. human immunodeficiency virus type 1 (HIV-1) RT). RTs lack proofreading activity and display high intrinsic error rates. Besides, high recombination rates observed in retroviruses are promoted by poor processivity that causes template switching, a hallmark of reverse transcription. HIV-1 RT inhibitors act-ing on its polymerase activity constitute the backbone of current antiretroviral therapies, although novel drugs, including ribonuclease H inhibitors, are still necessary to fight HIV infections. In Hepadnaviridae and Caulimoviridae, reverse transcription leads to the formation of nicked circular DNAs that will be converted into episomal DNA in the host cell nucleus. Structural and biochemical information on their polymerases is limited, although several drugs inhibiting HIV-1 RT are known to be effective against the human hepatitis B virus polymerase. In this review, we summarize current knowledge on reverse tran-scription in the five virus families and discuss available biochemical and structural information on RTs, including their biosynthesis, enzymatic activities, and potential inhibition. © 2016 Elsevier B.V. All rights reserved
publishDate 2016
dc.date.none.fl_str_mv 2016
2021
2021
2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
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dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/228549
url http://hdl.handle.net/10261/228549
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://dx.doi.org/10.1016/j.virusres.2016.12.019
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
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instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
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