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The nsP3 macro domain is important for Sindbis virus replication in neurons and neurovirulence in mice

Sindbis virus (SINV), the prototype alphavirus, contains a macro domain in the highly conserved N-terminal region of nonstructural protein 3 (nsP3). However, the biological role of the macro domain is unclear. Mutations of amino acids 10 and 24 from asparagine to alanine in the ADP-ribose binding re...

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Detalles Bibliográficos
Autores principales: Park, Eunhye, Griffin, Diane E.
Formato: Texto
Lenguaje:English
Publicado: Elsevier Inc. 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2683903/
https://www.ncbi.nlm.nih.gov/pubmed/19395054
http://dx.doi.org/10.1016/j.virol.2009.03.031
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author Park, Eunhye
Griffin, Diane E.
author_facet Park, Eunhye
Griffin, Diane E.
author_sort Park, Eunhye
collection PubMed
description Sindbis virus (SINV), the prototype alphavirus, contains a macro domain in the highly conserved N-terminal region of nonstructural protein 3 (nsP3). However, the biological role of the macro domain is unclear. Mutations of amino acids 10 and 24 from asparagine to alanine in the ADP-ribose binding region of the macro domain impaired SINV replication and viral RNA synthesis particularly in neurons, but did not alter binding of poly(ADP-ribose). Mutation at position 10 had the greatest effect and caused nsP3 instability in neurons, decreased SINV-induced death of mature, but not immature neurons, and attenuated virulence in 2 week-old, but not 5 day-old mice. A compensatory mutation at amino acid 31 in the macro domain of nsP3, as well as reversion of mutated amino acid 10, occurred during replication of double mutant SINV in vitro and in vivo. The nsP3 macro domain is important for SINV replication and age-dependent susceptibility to encephalomyelitis.
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spelling pubmed-26839032010-06-05 The nsP3 macro domain is important for Sindbis virus replication in neurons and neurovirulence in mice Park, Eunhye Griffin, Diane E. Virology Article Sindbis virus (SINV), the prototype alphavirus, contains a macro domain in the highly conserved N-terminal region of nonstructural protein 3 (nsP3). However, the biological role of the macro domain is unclear. Mutations of amino acids 10 and 24 from asparagine to alanine in the ADP-ribose binding region of the macro domain impaired SINV replication and viral RNA synthesis particularly in neurons, but did not alter binding of poly(ADP-ribose). Mutation at position 10 had the greatest effect and caused nsP3 instability in neurons, decreased SINV-induced death of mature, but not immature neurons, and attenuated virulence in 2 week-old, but not 5 day-old mice. A compensatory mutation at amino acid 31 in the macro domain of nsP3, as well as reversion of mutated amino acid 10, occurred during replication of double mutant SINV in vitro and in vivo. The nsP3 macro domain is important for SINV replication and age-dependent susceptibility to encephalomyelitis. Elsevier Inc. 2009-06-05 2009-04-23 /pmc/articles/PMC2683903/ /pubmed/19395054 http://dx.doi.org/10.1016/j.virol.2009.03.031 Text en Copyright © 2009 Elsevier Inc. All rights reserved. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle Article
Park, Eunhye
Griffin, Diane E.
The nsP3 macro domain is important for Sindbis virus replication in neurons and neurovirulence in mice
title The nsP3 macro domain is important for Sindbis virus replication in neurons and neurovirulence in mice
title_full The nsP3 macro domain is important for Sindbis virus replication in neurons and neurovirulence in mice
title_fullStr The nsP3 macro domain is important for Sindbis virus replication in neurons and neurovirulence in mice
title_full_unstemmed The nsP3 macro domain is important for Sindbis virus replication in neurons and neurovirulence in mice
title_short The nsP3 macro domain is important for Sindbis virus replication in neurons and neurovirulence in mice
title_sort nsp3 macro domain is important for sindbis virus replication in neurons and neurovirulence in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2683903/
https://www.ncbi.nlm.nih.gov/pubmed/19395054
http://dx.doi.org/10.1016/j.virol.2009.03.031
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