Loss of cytoskeletal transport during egress critically attenuates ectromelia virus infection in vivo

dc.contributor.authorLynn, Helena
dc.contributor.authorHorsington, Jacquelyn
dc.contributor.authorTer, Lee (Felix)
dc.contributor.authorHan, Shuyi
dc.contributor.authorChew, Yee Lian
dc.contributor.authorDiefenbach, Russell J
dc.contributor.authorWay, Michael
dc.contributor.authorChaudhri, Geeta
dc.contributor.authorKarupiah, Gunasegaran
dc.contributor.authorNewsome, Timothy
dc.date.accessioned2015-12-10T23:17:47Z
dc.date.issued2012
dc.date.updated2016-02-24T08:37:33Z
dc.description.abstractEgress of wrapped virus (WV) to the cell periphery following vaccinia virus (VACV) replication is dependent on interactions with the microtubule motor complex kinesin-1 and is mediated by the viral envelope protein A36. Here we report that ectromelia virus (ECTV), a related orthopoxvirus and the causative agent of mousepox, encodes an A36 homologue (ECTV-Mos-142) that is highly conserved despite a large truncation at the C terminus. Deleting the ECTV A36R gene leads to a reduction in the number of extracellular viruses formed and to a reduced plaque size, consistent with a role in microtubule transport. We also observed a complete loss of virus-associated actin comets, another phenotype dependent on A36 expression during VACV infection. ECTV ΔA36R was severely attenuated when used to infect the normally susceptible BALB/c mouse strain. ECTV ΔA36R replication and spread from the draining lymph nodes to the liver and spleen were significantly reduced in BALB/c mice and in Rag-1-deficient mice, which lack T and B lymphocytes. The dramatic reduction in ECTV ΔA36R titers early during the course of infection was not associated with an augmented immune response. Taken together, these findings demonstrate the critical role that subcellular transport pathways play not only in orthopoxvirus infection in an in vitro context but also during orthopoxvirus pathogenesis in a natural host. Furthermore, despite the attenuation of the mutant virus, we found that infection nonetheless induced protective immunity in mice, suggesting that orthopoxvirus vectors with A36 deletions may be considered another safe vaccine alternative.
dc.identifier.issn0022-538X
dc.identifier.urihttp://hdl.handle.net/1885/65348
dc.publisherAmerican Society for Microbiology
dc.rightsAuthor/s retain copyrighten_AU
dc.sourceJournal of Virology
dc.subjectKeywords: protein A36; unclassified drug; virus envelope protein; A36R gene; actin filament; animal cell; animal experiment; animal model; animal tissue; article; carboxy terminal sequence; cell loss; controlled study; embryo; female; gene deletion; gene function;
dc.titleLoss of cytoskeletal transport during egress critically attenuates ectromelia virus infection in vivo
dc.typeJournal article
dcterms.accessRightsOpen Accessen_AU
local.bibliographicCitation.issue13
local.bibliographicCitation.lastpage7443
local.bibliographicCitation.startpage7427
local.contributor.affiliationLynn, Helena, University of Sydney
local.contributor.affiliationHorsington, Jacquelyn, University of Sydney
local.contributor.affiliationTer, Lee (Felix), College of Medicine, Biology and Environment, ANU
local.contributor.affiliationHan, Shuyi, University of Sydney
local.contributor.affiliationChew, Yee Lian, University of Sydney
local.contributor.affiliationDiefenbach, Russell J, Westmead Millennium Institute
local.contributor.affiliationWay, Michael, Cancer Research UK
local.contributor.affiliationChaudhri, Geeta, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationKarupiah, Gunasegaran, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationNewsome, Timothy, University of Sydney
local.contributor.authoremailu4042418@anu.edu.au
local.contributor.authoruidTer, Lee (Felix), u4269320
local.contributor.authoruidChaudhri, Geeta, u4042418
local.contributor.authoruidKarupiah, Gunasegaran, u4039640
local.description.notesImported from ARIES
local.identifier.absfor110703 - Autoimmunity
local.identifier.absfor110704 - Cellular Immunology
local.identifier.ariespublicationf5625xPUB1092
local.identifier.citationvolume86
local.identifier.doi10.1128/JVI.06636-11
local.identifier.scopusID2-s2.0-84864125036
local.identifier.thomsonID000305501600039
local.identifier.uidSubmittedByf5625
local.type.statusPublished Version

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