Dermal infection with vaccinia virus reveals roles for virus proteins not seen using other inoculation routes.
Previously, we developed a model for testing the virulence and immunogenicity of vaccinia virus (VV) mutants based on the intradermal injection of BALB/c mouse ear pinnae. The model is characterized by a local infection in the inoculated skin without signs of systemic illness, mimicking dermal vaccination with VV. Here a further characterization of this model is presented, including the responses of mice to infectious virus doses as low as 10 p.f.u., a quantification of the infiltrate at the site of infection and use of different virus and mouse strains. The model was then used to compare the pathogenesis of six mutants of VV strain Western Reserve (WR) lacking genes A36R, A40R, A44L, B12R, B13R or B15R with that of appropriate control viruses. All of these genes except B12R and B15R influence the outcome of dermal infection with WR and for A40R and B13R this is the first role that has been reported after infection of mammals. A comparison of new and published results from intradermal and intranasal models is presented, showing that out of 16 gene deletion or insertion mutants of VV, half have phenotypes distinct from controls in only one of these models. Thus, the intranasal and intradermal models are complementary tools for dissecting the genetic basis of VV virulence.
Department of Virology, The Wright-Fleming Institute, Faculty of Medicine, Imperial College, St Mary's Campus, Norfolk Place, London W2 1PG, UK2.|Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK1.
David C
DC
Tscharke
Department of Virology, The Wright-Fleming Institute, Faculty of Medicine, Imperial College, St Mary's Campus, Norfolk Place, London W2 1PG, UK2.|Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK1.
Patrick C
PC
Reading
Department of Virology, The Wright-Fleming Institute, Faculty of Medicine, Imperial College, St Mary's Campus, Norfolk Place, London W2 1PG, UK2.|Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK1.
Geoffrey L
GL
Smith
D000367:Age Factors; D000818:Animals; D004195:Disease Models, Animal; D004423:Ear / Q000821:virology; D017353:Gene Deletion; D006801:Humans; D007271:Injections, Intradermal; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D017193:Skin Diseases, Viral / Q000503:physiopathology / Q000821:virology*; D014615:Vaccinia / Q000503:physiopathology* / Q000821:virology; D014616:Vaccinia virus / Q000145:classification / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D014774:Virulence / Q000235:genetics
D014764:Viral Proteins