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Analysis of A47, an Immunoprevalent Protein of Vaccinia Virus, leads to a reevaluation of the total antiviral CD8+ T cell response

Yuen, Tracy; Flesch, Inge; Hollett (previously Noel), Natasha; Dobson, Bianca; Russell, Tiffany; Fahrer, Aude; Tscharke, David

Description

Vaccinia virus (VACV) is the prototypic orthopoxvirus and was the live vaccine used to eradicate smallpox. In addition, VACV is a possible vector for recombinant vaccines. Despite these reasons for study, the roles of many VACV genes are unknown, and some fundamental aspects, such as the total size of immune responses, remain poorly characterized. VACV gene A47L is of interest because it is highly transcribed, has no sequence similarity to any nonpoxvirus gene, and contains a...[Show more]

dc.contributor.authorYuen, Tracy
dc.contributor.authorFlesch, Inge
dc.contributor.authorHollett (previously Noel), Natasha
dc.contributor.authorDobson, Bianca
dc.contributor.authorRussell, Tiffany
dc.contributor.authorFahrer, Aude
dc.contributor.authorTscharke, David
dc.date.accessioned2015-12-08T22:23:03Z
dc.identifier.issn0022-538X
dc.identifier.urihttp://hdl.handle.net/1885/32707
dc.description.abstractVaccinia virus (VACV) is the prototypic orthopoxvirus and was the live vaccine used to eradicate smallpox. In addition, VACV is a possible vector for recombinant vaccines. Despite these reasons for study, the roles of many VACV genes are unknown, and some fundamental aspects, such as the total size of immune responses, remain poorly characterized. VACV gene A47L is of interest because it is highly transcribed, has no sequence similarity to any nonpoxvirus gene, and contains a larger-than-expected number of CD8+ T cell epitopes. Here it is shown that A47L is not required for growth in vitro and does not contribute to virulence in mice. However, we confirmed that this one protein primes CD8+ T cells to three different epitopes in C57BL/6 mice. In the process, one of these epitopes was redefined and shown to be the most dominant in A47 and one of the more highly ranked in VACV as a whole. The relatively high immunogenicity of this epitope led to a reevaluation of the total CD8+ T cell response to VACV. By the use of two methods, the true size of the response was found to be around double previous estimates and at its peak is on the order of 60% of all CD8+ T cells. We speculate that more CD8+ T cell epitopes remain to be mapped for VACV and that underestimation of responses is unlikely to be unique to VACV, so there would be merit in revisiting this issue for other viruses.
dc.publisherAmerican Society for Microbiology
dc.sourceJournal of Virology
dc.subjectKeywords: a47 protein; CD8 antigen; epitope; unclassified drug; virus protein; article; C57BL 6 mouse; CD8+ T lymphocyte; controlled study; female; immune response; immunogenicity; mouse; nonhuman; priority journal; protein analysis; Vaccinia virus; virus gene; Ami
dc.titleAnalysis of A47, an Immunoprevalent Protein of Vaccinia Virus, leads to a reevaluation of the total antiviral CD8+ T cell response
dc.typeJournal article
local.description.notesImported from ARIES
local.identifier.citationvolume84
dc.date.issued2010
local.identifier.absfor110704 - Cellular Immunology
local.identifier.absfor060506 - Virology
local.identifier.ariespublicationu8611701xPUB94
local.type.statusPublished Version
local.contributor.affiliationYuen, Tracy, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationFlesch, Inge, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationHollett (previously Noel), Natasha, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationDobson, Bianca, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationRussell, Tiffany, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationFahrer, Aude, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationTscharke, David, College of Medicine, Biology and Environment, ANU
local.description.embargo2037-12-31
local.bibliographicCitation.issue19
local.bibliographicCitation.startpage10220
local.bibliographicCitation.lastpage10229
local.identifier.doi10.1128/JVI.01281-10
local.identifier.absseo920108 - Immune System and Allergy
dc.date.updated2016-02-24T11:42:51Z
local.identifier.scopusID2-s2.0-77956806285
local.identifier.thomsonID000282641800053
CollectionsANU Research Publications

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