Six host-range restricted poxviruses from three genera induce distinct gene expression profiles in an in vivo mouse model

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dc.contributor.authorOfferman, Kristyen_ZA
dc.contributor.authorDeffur, Arminen_ZA
dc.contributor.authorCarulei, Oliviaen_ZA
dc.contributor.authorWilkinson, Roberten_ZA
dc.contributor.authorDouglass, Nicolaen_ZA
dc.contributor.authorWilliamson, Anna Liseen_ZA
dc.date.accessioned2015-12-07T08:49:41Z
dc.date.available2015-12-07T08:49:41Z
dc.date.issued2015en_ZA
dc.description.abstractBACKGROUND: Host-range restricted poxviruses make promising vaccine vectors due to their safety profile and immunogenicity. An understanding of the host innate immune responses produced by different poxvirus vectors would aid in the assessment, selection and rational design of improved vaccines for human and veterinary applications. Novel avipoxviruses are being assessed to determine if they are different from other poxvirus vectors. Analysis of the transcriptome induced in a mouse model would aid in determining if there were significant differences between different poxvirus vectors which may reflect different adjuvant potential as well as establish if they should be further evaluated as vaccine vectors. RESULTS: We compared host transcript abundance in the spleens of BALB/c mice twenty four hours after intravenous infection (10 5 pfu/mouse) with six host-restricted poxvirus species from three genera, namely Lumpy Skin Disease virus (LSDV), Canarypox virus (CNPV), Fowlpox virus (FWPV), modified vaccinia Ankara (MVA) and two novel South African avipoxviruses, Feral Pigeonpox virus (FeP2) and Penguinpox virus (PEPV). These six viruses produced qualitatively and quantitatively distinct host responses with LSDV, followed by MVA, inducing the greatest interferon (IFN) response. FeP2 and PEPV caused very little change to host transcript abundance compared to the other 4 viruses tested. CNPV and FWPV induced the up regulation of two immunoglobulin genes (Ighg and Ighg3 (IgG3)) with CNPV inducing a third, Ighm (IgM). HIV-1-specific IgG3 antibodies have been correlated with decreased risk of HIV-1 infection in the RV144 trial, which included a CNPV-based vector (Yates et al. (Sci Transl Med, 6(228) p228, 2014). Up regulation of IgG3 by CNPV and FWPV but not the other poxviruses tested in vivo, implies that these two avipoxvirus-vector backbones may be involved in stimulation of the clinically important IgG3 antibody subclass. Differential transcript abundance associated with the different poxviruses is further discussed with particular emphasis on responses related to immune responses. CONCLUSION: Six, genetically diverse host-restricted poxviruses produce different responses in a mouse model early after infection. These differences may affect the immune response induced to vaccine antigen in vectors based on these viruses. The two novel avipoxviruses were clearly distinguishable from the other viruses.en_ZA
dc.identifier.apacitationOfferman, K., Deffur, A., Carulei, O., Wilkinson, R., Douglass, N., & Williamson, A. L. (2015). Six host-range restricted poxviruses from three genera induce distinct gene expression profiles in an in vivo mouse model. <i>BMC Genomics</i>, http://hdl.handle.net/11427/15638en_ZA
dc.identifier.chicagocitationOfferman, Kristy, Armin Deffur, Olivia Carulei, Robert Wilkinson, Nicola Douglass, and Anna Lise Williamson "Six host-range restricted poxviruses from three genera induce distinct gene expression profiles in an in vivo mouse model." <i>BMC Genomics</i> (2015) http://hdl.handle.net/11427/15638en_ZA
dc.identifier.citationOfferman, K., Deffur, A., Carulei, O., Wilkinson, R., Douglass, N., & Williamson, A. L. (2015). Six host-range restricted poxviruses from three genera induce distinct gene expression profiles in an in vivo mouse model. BMC genomics, 16(1), 510.en_ZA
dc.identifier.ris TY - Journal Article AU - Offerman, Kristy AU - Deffur, Armin AU - Carulei, Olivia AU - Wilkinson, Robert AU - Douglass, Nicola AU - Williamson, Anna Lise AB - BACKGROUND: Host-range restricted poxviruses make promising vaccine vectors due to their safety profile and immunogenicity. An understanding of the host innate immune responses produced by different poxvirus vectors would aid in the assessment, selection and rational design of improved vaccines for human and veterinary applications. Novel avipoxviruses are being assessed to determine if they are different from other poxvirus vectors. Analysis of the transcriptome induced in a mouse model would aid in determining if there were significant differences between different poxvirus vectors which may reflect different adjuvant potential as well as establish if they should be further evaluated as vaccine vectors. RESULTS: We compared host transcript abundance in the spleens of BALB/c mice twenty four hours after intravenous infection (10 5 pfu/mouse) with six host-restricted poxvirus species from three genera, namely Lumpy Skin Disease virus (LSDV), Canarypox virus (CNPV), Fowlpox virus (FWPV), modified vaccinia Ankara (MVA) and two novel South African avipoxviruses, Feral Pigeonpox virus (FeP2) and Penguinpox virus (PEPV). These six viruses produced qualitatively and quantitatively distinct host responses with LSDV, followed by MVA, inducing the greatest interferon (IFN) response. FeP2 and PEPV caused very little change to host transcript abundance compared to the other 4 viruses tested. CNPV and FWPV induced the up regulation of two immunoglobulin genes (Ighg and Ighg3 (IgG3)) with CNPV inducing a third, Ighm (IgM). HIV-1-specific IgG3 antibodies have been correlated with decreased risk of HIV-1 infection in the RV144 trial, which included a CNPV-based vector (Yates et al. (Sci Transl Med, 6(228) p228, 2014). Up regulation of IgG3 by CNPV and FWPV but not the other poxviruses tested in vivo, implies that these two avipoxvirus-vector backbones may be involved in stimulation of the clinically important IgG3 antibody subclass. Differential transcript abundance associated with the different poxviruses is further discussed with particular emphasis on responses related to immune responses. CONCLUSION: Six, genetically diverse host-restricted poxviruses produce different responses in a mouse model early after infection. These differences may affect the immune response induced to vaccine antigen in vectors based on these viruses. The two novel avipoxviruses were clearly distinguishable from the other viruses. DA - 2015 DB - OpenUCT DO - 10.1186/s12864-015-1659-1 DP - University of Cape Town J1 - BMC Genomics LK - https://open.uct.ac.za PB - University of Cape Town PY - 2015 T1 - Six host-range restricted poxviruses from three genera induce distinct gene expression profiles in an in vivo mouse model TI - Six host-range restricted poxviruses from three genera induce distinct gene expression profiles in an in vivo mouse model UR - http://hdl.handle.net/11427/15638 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/15638
dc.identifier.urihttp://dx.doi.org/10.1186/s12864-015-1659-1
dc.identifier.vancouvercitationOfferman K, Deffur A, Carulei O, Wilkinson R, Douglass N, Williamson AL. Six host-range restricted poxviruses from three genera induce distinct gene expression profiles in an in vivo mouse model. BMC Genomics. 2015; http://hdl.handle.net/11427/15638.en_ZA
dc.language.isoengen_ZA
dc.publisherBioMed Central Ltden_ZA
dc.publisher.departmentInstitute of Infectious Disease and Molecular Medicineen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an Open Access article distributed under the terms of the Creative Commons Attribution Licenseen_ZA
dc.rights.holder2015 Offerman et al.en_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourceBMC Genomicsen_ZA
dc.source.urihttp://www.biomedcentral.com/bmcgenomics/en_ZA
dc.subject.otherPoxvirusen_ZA
dc.subject.otherVaccineen_ZA
dc.subject.otherMicro-arrayen_ZA
dc.subject.otherLSDVen_ZA
dc.subject.otherMVAen_ZA
dc.subject.otherAvipoxvirusesen_ZA
dc.titleSix host-range restricted poxviruses from three genera induce distinct gene expression profiles in an in vivo mouse modelen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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