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JL Taylor, K Wilcox; SP100B, a Component of the Innate Immune System That Inhibits Expression of Exogenous Genes . Invest. Ophthalmol. Vis. Sci. 2002;43(13):4318.
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© ARVO (1962-2015); The Authors (2016-present)
Herpes simplex virus (HSV) DNA localizes in infected cell nuclei adjacent to protein complexes termed ND10s where virus transcription then begins. It has been hypothesized that ND10s are sites of innate immune suppression of viral gene expression. We have shown that human corneal cells have ND10s that are larger and more abundant than other cell types examined. Purpose: To determine whether proteins found in ND10s are able to inhibit viral gene expression. Method: Plasmids expressing individual genes encoding ND10 proteins, including splice variants PML and SP100, were co-transfected into cells with plasmids expressing viral genes or reporter genes from viral promoters. Gene expression was evaluated by chemiluminescent detection of reporter gene products (beta-galactosidase or luciferase) and immunofluorescence was used to determine the localization of gene products. Results: One variant of the SP100 protein, SP100B, but neither SP100A nor either of two variants of PML protein inhibited expression from DNA on co-transfected plasmids. SP100B inhibited basal as well as transactivated expression from both viral and cellular promoters. This repressive activity required the presence of a 30 aa region in the C-terminus of SP100B. In cells that were transfected with plasmids expressing ND10 proteins or in cells stably expressing green fluorescent protein-tagged ND10 proteins, PML variants and SP100A co-localized. Suprisingly, SP100B did not completely co-localize with other ND10 proteins. Conclusions: SP100B, a variant of the ND10-localized protein SP100A reported to be enhanced in expression by interferons, is a potent inhibitor of gene expression from exogenous DNA, including the transactivated expression of HSV genes and may play an important role in inhibiting virus proliferation.
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