The vaccinia virus C12L protein inhibits mouse IL-18 and promotes virus virulence in the murine intranasal model

Julian A. Symons, Elizabeth Adams, David C. Tscharke, Patrick C. Reading, Herman Waldmann, Geoffrey L. Smith*

*Corresponding author for this work

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68 Citations (Scopus)


A bioassay that measured the interleukin (IL)-12-induced production of interferon (IFN)-γ from mouse splenocytes was used to identify a soluble factor in the supernatants of vaccinia virus (VV)-infected cells that inhibited the production of IFN-γ. This soluble factor was expressed by 14 out of 16 VV strains including the Western Reserve (WR) strain, but strains Copenhagen and Tashkent and a mutant of strain WR called 6/2 lacked this activity. The gene encoding this activity was identified as C12L by transferring DNA present in VV WR but missing in VV WR 6/2 into VV Copenhagen and testing for expression of the soluble factor. The C12L protein shows amino acid similarity to IL-18 binding proteins that are encoded by poxviruses, mice and humans, and C12L protein produced from VV or baculovirus inhibited the biological activity of mouse IL-18 in vitro. Thus the inhibition of IL-12-induced IFN-γ production was due to indirect effects of C12L on IL-18, illustrating the synergistic action of these pro-inflammatory cytokines. To study the role of the C12L protein in the virus life-cycle, we constructed a deletion mutant lacking the C12L gene and a revertant virus in which the gene was reinserted into the deletion mutant. In vitro the replication and plaque size of these viruses were indistinguishable. However, infection of BALB/c mice by the intranasal route showed that the deletion mutant was attenuated and induced lower weight loss and signs of illness compared to controls.

Original languageEnglish
Pages (from-to)2833-2844
Number of pages12
JournalJournal of General Virology
Issue number11
Publication statusPublished - 1 Nov 2002
Externally publishedYes


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