title: Six host-range restricted poxviruses from three genera induce distinct gene expression profiles in an in vivo mouse model.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Medical Virology, Department of Clinical Laboratory Sciences, University of Cape Town, Cape Town, South Africa. kristymareeofferman@gmail.com.|Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa. kristymareeofferman@gmail.com.
authors.forename: Kristy
authors.initials: K
authors.lastname: Offerman
authors.affiliation: Clinical Infectious Diseases Research Initiative, University of Cape Town, Cape Town, South Africa. armin.deffur@gmail.com.|Department of Medicine, University of Cape Town, Cape Town, South Africa. armin.deffur@gmail.com.
authors.forename: Armin
authors.initials: A
authors.lastname: Deffur
authors.affiliation: Division of Medical Virology, Department of Clinical Laboratory Sciences, University of Cape Town, Cape Town, South Africa. ocarulei@gmail.com.|Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa. ocarulei@gmail.com.
authors.forename: Olivia
authors.initials: O
authors.lastname: Carulei
authors.affiliation: Clinical Infectious Diseases Research Initiative, University of Cape Town, Cape Town, South Africa. robert.wilkinson@uct.ac.za.|Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa. robert.wilkinson@uct.ac.za.|The Francis Crick Institute Mill Hill Laboratory, London, NW7 1AA, UK. robert.wilkinson@uct.ac.za.|Department of Medicine, Imperial College, London, W2 1PG, UK. robert.wilkinson@uct.ac.za.
authors.forename: Robert
authors.initials: R
authors.lastname: Wilkinson
authors.affiliation: Division of Medical Virology, Department of Clinical Laboratory Sciences, University of Cape Town, Cape Town, South Africa. niki.douglass@uct.ac.za.|Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa. niki.douglass@uct.ac.za.
authors.forename: Nicola
authors.initials: N
authors.lastname: Douglass
authors.affiliation: Division of Medical Virology, Department of Clinical Laboratory Sciences, University of Cape Town, Cape Town, South Africa. anna-lise.williamson@uct.ac.za.|Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa. anna-lise.williamson@uct.ac.za.|National Health Laboratory Service, Groote Schuur Hospital, Cape Town, South Africa. anna-lise.williamson@uct.ac.za.
authors.forename: Anna-Lise
authors.initials: AL
authors.lastname: Williamson
mesh_terms: D000818:Animals; D005260:Female; D005822:Genetic Vectors / Q000235:genetics; D015658:HIV Infections / Q000235:genetics; D015497:HIV-1 / Q000472:pathogenicity; D058507:Host Specificity / Q000235:genetics*; D006801:Humans; D007074:Immunoglobulin G / Q000235:genetics; D007372:Interferons / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D011212:Poxviridae / Q000235:genetics*; D059467:Transcriptome / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics; D014612:Vaccines / Q000235:genetics
chemical_list: D007074:Immunoglobulin G; D014612:Vaccines; D007372:Interferons