Critical role for the oligoadenylate synthetase/RNase L pathway in response to IFN-β during acute ocular herpes simplex virus type 1 infection
Austin, B.A., James, C., Silverman, R.H. and Carr, D.J.J. (2005) Critical role for the oligoadenylate synthetase/RNase L pathway in response to IFN-β during acute ocular herpes simplex virus type 1 infection. Journal of Immunology, 175 (2). pp. 1100-1106.
*No subscription required
We previously demonstrated that IFN-β transgene treatment protects mouse trigeminal ganglia (TG) cells from acute HSV-1 infection in vitro. However, IFN-α6 transgene treatment does not provide protection against acute HSV-1 infection in vitro, even though equivalent levels of IFN are expressed with both transgene treatments. In the present study we show that IFN-β transgene treatment before acute ocular HSV-1 infection protects mice from HSV-1-mediated mortality, whereas IFN-α6 transgene treatment does not reduce mortality. Treatment with the IFN-β and IFN-α6 transgenes was associated with increased expression of oligoadenylate synthetase (OAS)1a mRNA in the eye. However, protein kinase R mRNA was not up-regulated in the eye. In TG, only IFN-β transgene treatment reduced infectious virus levels. Furthermore, in the absence of a functional OAS pathway, corneal HSV-1 Ag expression was more widespread, and the ability of IFN-β transgene treatment to reduce infectious HSV-1 in eyes and TG was lost. Along with selective up-regulation of OAS1a mRNA expression in TG from IFN-β transgene-treated mice, we found increased levels of phospho-STAT1. Likewise, p38 MAPK phosphorylation was increased in TG from IFN-β transgene-treated mice, compared with both IFN-α6 and vector-treated mice. We also observed a time-dependent increase in JNK phosphorylation in TG from IFN-β transgene-treated vs IFN-α6 and vector-treated mice. Our results demonstrate that IFN-β is a potent antiviral cytokine that exerts protection against ocular HSV-1 infection via selective up-regulation of OAS1a mRNA in TG and by altering the phosphorylation of proteins in antiviral signaling cascades.
|Publication Type:||Journal Article|
|Murdoch Affiliation:||School of Veterinary and Biomedical Sciences|
|Publisher:||The American Association of Immunologists, Inc.|
|Copyright:||© 2005 by The American Association of Immunologists, Inc.|
|Item Control Page|