A homolog of the variola virus B22 membrane protein contributes to ectromelia virus pathogenicity in the mouse footpad model

• Published in: Virology (New York, N.Y.) Vol. 501; pp. 107 - 114
• Main Authors: Reynolds, Sara E, Earl, Patricia L, Minai, Mahnaz, Moore, Ian, Moss, Bernard
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.01.2017
• Subjects: Animals; Disease Models, Animal; Ectromelia virus; Ectromelia virus - genetics; Ectromelia virus - metabolism; Ectromelia virus - pathogenicity; Ectromelia, Infectious - genetics; Ectromelia, Infectious - metabolism; Ectromelia, Infectious - pathology; Ectromelia, Infectious - virology; Female; Host defense; Humans; Infectious Disease; Innate immunity; Liver - pathology; Liver - virology; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mice; Mice, Inbred BALB C; Poxvirus; Spleen - pathology; Spleen - virology; T cells; Variola virus - genetics; Variola virus - metabolism; Viral pathogenicity; Viral Proteins - genetics; Viral Proteins - metabolism; Virulence; Innate immunity; Poxvirus; Host defense; Ectromelia virus; T cells; Viral pathogenicity
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1016/j.virol.2016.11.010

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.