title: A homolog of the variola virus B22 membrane protein contributes to ectromelia virus pathogenicity in the mouse footpad model.
abstract: Most poxviruses encode a homolog of a ~200,000-kDa membrane protein originally identified in variola virus. We investigated the importance of the ectromelia virus (ECTV) homolog C15 in a natural infection model. In cultured mouse cells, the replication of a mutant virus with stop codons near the N-terminus (ECTV-C15Stop) was indistinguishable from a control virus (ECTV-C15Rev). However, for a range of doses injected into the footpads of BALB/c mice there was less mortality with the mutant. Similar virus loads were present at the site of infection with mutant or control virus whereas there was less ECTV-C15Stop in popliteal and inguinal lymph nodes, spleen and liver indicating decreased virus spread and replication. The latter results were supported by immunohistochemical analyses. Decreased spread was evidently due to immune modulatory activity of C15, rather than to an intrinsic viral function, as the survival of infected mice depended on CD4+ and CD8+ T cells.
authors.affiliation: Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; Fairleigh Dickinson University, 285 Madison Avenue, Madison, NJ 07940, USA.
authors.forename: Sara E
authors.initials: SE
authors.lastname: Reynolds
authors.affiliation: Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Patricia L
authors.initials: PL
authors.lastname: Earl
authors.affiliation: Comparative Medicine Branch, Infectious Disease Pathogenesis Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Mahnaz
authors.initials: M
authors.lastname: Minai
authors.affiliation: Comparative Medicine Branch, Infectious Disease Pathogenesis Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Ian
authors.initials: I
authors.lastname: Moore
authors.affiliation: Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: bmoss@nih.gov.
authors.forename: Bernard
authors.initials: B
authors.lastname: Moss
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004481:Ectromelia virus / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D004482:Ectromelia, Infectious / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000821:virology*; D005260:Female; D006801:Humans; D008099:Liver / Q000473:pathology / Q000821:virology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000473:pathology / Q000821:virology; D012901:Variola virus / Q000235:genetics / Q000378:metabolism; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D014774:Virulence
chemical_list: D008565:Membrane Proteins; D014764:Viral Proteins
keywords: Ectromelia virus; Host defense; Innate immunity; Poxvirus; T cells; Viral pathogenicity