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Critical role for the oligoadenylate synthetase/RNase L pathway in response to IFN-β during acute ocular herpes simplex virus type 1 infection
Journal article   Peer reviewed

Critical role for the oligoadenylate synthetase/RNase L pathway in response to IFN-β during acute ocular herpes simplex virus type 1 infection

B.A. Austin, C. James, R.H. Silverman and D.J.J. Carr
Journal of Immunology, Vol.175(2), pp.1100-1106
2005
DOI: https://doi.org/10.1016/0013-4686(91)85130-Y
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Abstract

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.

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2 Chemistry
2.145 Biosensors
2.145.561 Anodic Stripping Voltammetry
Web Of Science research areas
Electrochemistry
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Chemistry
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