Skip to main content
. 2011 Feb 9;6(2):e16870. doi: 10.1371/journal.pone.0016870

Figure 8. Model of VZV-mediated interference with IRF3 activation.

Figure 8

Upon VZV entry, the viral kinase ORF47p, which is part of the VZV tegument, is released in the cytoplasm where it can encounter IRF3 and induce its atypical phosphorylation leading to an up-shift in the electrophoretic mobility of IRF3. Our data demonstrated that VZV does not activate the cellular kinase TBK1 and that VZV ORF47p-mediated phosphorylation of IRF3 does not occur on the classical serine 396. Furthermore, this atypical phosphorylation does not allow IRF3 homodimerization and subsequent induction of target genes such as IFN-β and ISG15. Consequently, the phosphorylated forms of IRF3 engendered by VZV through its ORF47 kinase, even if leading to an up-shift in SDS-PAGE, have to be distinguished from the hyperphosphorylated forms III and IV induced by other viruses such as the Sendai Virus. In addition, we have shown, in cells infected with a mutant virus unable to express the viral kinase ORF47, that the phosphorylation of IRF3 on serine 396 is restored. Hence, IRF3 homodimerizes again in cells infected with this ORF47 deficient virus. However, we failed to detect an up-shift of IRF3 in SDS-PAGE in these infected cells. Surprisingly, IRF3 showed the same behaviour in response to Poly (I:C) treatment suggesting that IRF3 phosphorylation on serine 396 and subsequent homodimerization are not necessarily accompanied with an up-shift in SDS-PAGE as observed in the context of an infection with the Sendai Virus. This also suggests that another activated form of IRF3, different than the forms III and IV, can exist. Until now, we still do not know whether ORF47p requires other viral proteins such as IE62 to mediate IRF3 phosphorylation following VZV infection. We also do not know whether this phosphorylation occurs at the C- or N-terminus of IRF3. Finally, we have shown that VZV inhibits the activation of NF-κB and that this inhibition is independent on the viral kinase ORF47p. In conclusion, we propose a model in which VZV interferes with the activation of IRF3 and subsequent induction of the antiviral response through its kinase ORF47p.