Nuclear Herpesvirus Capsid Motility Is Not Dependent on F-Actin

ABSTRACT A considerable part of the herpesvirus life cycle takes place in the host nucleus. While much progress has been made to understand the molecular processes required for virus replication in the nucleus, much less is known about the temporal and spatial dynamics of these events. Previous stud...

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Autores principales:	Jens B. Bosse, Stina Virding, Stephan Y. Thiberge, Julian Scherer, Harald Wodrich, Zsolt Ruzsics, Ulrich H. Koszinowski, Lynn W. Enquist
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2014
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/9ce4c3c01c6c484aaa388b0500a3b027
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spelling	oai:doaj.org-article:9ce4c3c01c6c484aaa388b0500a3b0272021-11-15T15:45:55ZNuclear Herpesvirus Capsid Motility Is Not Dependent on F-Actin10.1128/mBio.01909-142150-7511https://doaj.org/article/9ce4c3c01c6c484aaa388b0500a3b0272014-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01909-14https://doaj.org/toc/2150-7511ABSTRACT A considerable part of the herpesvirus life cycle takes place in the host nucleus. While much progress has been made to understand the molecular processes required for virus replication in the nucleus, much less is known about the temporal and spatial dynamics of these events. Previous studies have suggested that nuclear capsid motility is directed and dependent on actin filaments (F-actin), possibly using a myosin-based, ATP-dependent mechanism. However, the conclusions from these studies were indirect. They either relied on the effects of F-actin depolymerizing drugs to deduce an F-actin dependency or they visualized nuclear F-actin but failed to show a direct link to capsid motility. Moreover, no direct link between nuclear capsid motility and a molecular motor has been established. In this report, we reinvestigate the involvement of F-actin in nuclear herpesvirus capsid transport. We show for representative members of all three herpesvirus subfamilies that nuclear capsid motility is not dependent on nuclear F-actin and that herpesvirus infection does not induce nuclear F-actin in primary fibroblasts. Moreover, in these cells, three F-actin-inhibiting drugs failed to effect capsid motility. Only latrunculin A treatment stalled nuclear capsids but did so by an unexpected effect: the drug induced actin rods in the nucleus. Immobile capsids accumulated around actin rods, and immunoprecipitation experiments suggested that capsid motility stopped because latrunculin-induced actin rods nonspecifically bind nuclear capsids. Interestingly, capsid motility was unaffected in cells that do not induce actin rods. Based on these data, we conclude that herpesvirus nuclear capsid motility is not dependent on F-actin. IMPORTANCE Herpesviruses are large DNA viruses whose replication is dependent on the host nucleus. However, we do not understand how key nuclear processes, including capsid assembly, genome replication, capsid packaging, and nuclear egress, are dynamically connected in space and time. Fluorescence live-cell microscopy revealed that nuclear capsids are highly mobile early in infection. Two studies suggested that this motility might be due to active myosin-based transport of capsids on nuclear F-actin. However, direct evidence for such motor-based transport is lacking. We revisited this phenomenon and found no evidence that nuclear capsid motility depended on F-actin. Our results reopen the question of how nuclear herpesvirus capsids move in the host nucleus.Jens B. BosseStina VirdingStephan Y. ThibergeJulian SchererHarald WodrichZsolt RuzsicsUlrich H. KoszinowskiLynn W. EnquistAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 5, Iss 5 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Jens B. Bosse Stina Virding Stephan Y. Thiberge Julian Scherer Harald Wodrich Zsolt Ruzsics Ulrich H. Koszinowski Lynn W. Enquist Nuclear Herpesvirus Capsid Motility Is Not Dependent on F-Actin
description	ABSTRACT A considerable part of the herpesvirus life cycle takes place in the host nucleus. While much progress has been made to understand the molecular processes required for virus replication in the nucleus, much less is known about the temporal and spatial dynamics of these events. Previous studies have suggested that nuclear capsid motility is directed and dependent on actin filaments (F-actin), possibly using a myosin-based, ATP-dependent mechanism. However, the conclusions from these studies were indirect. They either relied on the effects of F-actin depolymerizing drugs to deduce an F-actin dependency or they visualized nuclear F-actin but failed to show a direct link to capsid motility. Moreover, no direct link between nuclear capsid motility and a molecular motor has been established. In this report, we reinvestigate the involvement of F-actin in nuclear herpesvirus capsid transport. We show for representative members of all three herpesvirus subfamilies that nuclear capsid motility is not dependent on nuclear F-actin and that herpesvirus infection does not induce nuclear F-actin in primary fibroblasts. Moreover, in these cells, three F-actin-inhibiting drugs failed to effect capsid motility. Only latrunculin A treatment stalled nuclear capsids but did so by an unexpected effect: the drug induced actin rods in the nucleus. Immobile capsids accumulated around actin rods, and immunoprecipitation experiments suggested that capsid motility stopped because latrunculin-induced actin rods nonspecifically bind nuclear capsids. Interestingly, capsid motility was unaffected in cells that do not induce actin rods. Based on these data, we conclude that herpesvirus nuclear capsid motility is not dependent on F-actin. IMPORTANCE Herpesviruses are large DNA viruses whose replication is dependent on the host nucleus. However, we do not understand how key nuclear processes, including capsid assembly, genome replication, capsid packaging, and nuclear egress, are dynamically connected in space and time. Fluorescence live-cell microscopy revealed that nuclear capsids are highly mobile early in infection. Two studies suggested that this motility might be due to active myosin-based transport of capsids on nuclear F-actin. However, direct evidence for such motor-based transport is lacking. We revisited this phenomenon and found no evidence that nuclear capsid motility depended on F-actin. Our results reopen the question of how nuclear herpesvirus capsids move in the host nucleus.
format	article
author	Jens B. Bosse Stina Virding Stephan Y. Thiberge Julian Scherer Harald Wodrich Zsolt Ruzsics Ulrich H. Koszinowski Lynn W. Enquist
author_facet	Jens B. Bosse Stina Virding Stephan Y. Thiberge Julian Scherer Harald Wodrich Zsolt Ruzsics Ulrich H. Koszinowski Lynn W. Enquist
author_sort	Jens B. Bosse
title	Nuclear Herpesvirus Capsid Motility Is Not Dependent on F-Actin
title_short	Nuclear Herpesvirus Capsid Motility Is Not Dependent on F-Actin
title_full	Nuclear Herpesvirus Capsid Motility Is Not Dependent on F-Actin
title_fullStr	Nuclear Herpesvirus Capsid Motility Is Not Dependent on F-Actin
title_full_unstemmed	Nuclear Herpesvirus Capsid Motility Is Not Dependent on F-Actin
title_sort	nuclear herpesvirus capsid motility is not dependent on f-actin
publisher	American Society for Microbiology
publishDate	2014
url	https://doaj.org/article/9ce4c3c01c6c484aaa388b0500a3b027
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Nuclear Herpesvirus Capsid Motility Is Not Dependent on F-Actin

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