It study did not reproduce the results of that report

HSV 2 prevents IFN mediated induction of ISGs in primary human skin fibroblasts In cultured cells, BAM7 Herpes simplex viruses are somewhat resistant to the antiviral ramifications of type I IFN treatment. IFNs help inhibition of viral replication and viral protein translation through the transactivation of various ISGs. Consequently, the ability of HSV 2 to inhibit IFN mediated induction of ISG expression was analyzed following infection of primary human dermal fibroblasts. Therapy of uninfected HDFas using IFNB upregulated STAT1 expression, an element of the IFN signaling cascade, and stimulated expression of the mobile ISGs, Mx1 and ISG15. On the other hand, in HSV 2 infected cells IFNB treatment did not upregulate STAT1 and was unable to transactivate expression of both Mx1 or ISG15.

This information shows that HSV 2 encodes at least one mechanism for subversion of IFN mediated induction of cellular intrinsic antiviral pathways. 3. 2. Therefore, the power of HSV 2 to prevent transactivation Metastasis of antiviral ISG expression and thereby IFN mediated JAK STAT signaling was evaluated in quite a few transformed cell lines. Most cell lines infected with HSV 2 showed a marked decrease at 16 hpi in their power to activate IFN mediated transcriptional activation of the kind I IFN dependent ISRE promoter. However, with respect to the cell line infected, a variation in the replicative cycle where HSV 2 inhibits the IFN signaling cascade was seen. In 293A and HeLa cells, HSV 2s ability to abrogate IFN signaling was not affected by inhibition of HSV 2 replication by often PAA or acyclovir.

This data shows that early viral proteins, or dripping late viral proteins, are entirely effective at inhibiting IFN signaling in these cell lines, since each PAA and acyclovir inhibit thereby viral DNA replication and late viral NSC 405020 gene expression. Therefore, late viral gene products or late started cell functions should compensate for these inadequacies. Despite the specific differences in the HSV 2 replicative stage that mediated inhibition of IFN signaling, there were no obvious differences between cell lines within the kinetics with which IFN signaling was inhibited by HSV 2. All cell lines examined demonstrated a precipitous inhibition of IFN signaling between 4 and 8 hpi with almost complete abolition of signaling by 16 hpi. Taken together, this data suggests that HSV 2 encodes the capability to affect IFN signaling pathways both ahead of and subsequent viral DNA replication and that HSV 2 appears to affect IFN mediated steps through distinctly different, but compensatory systems.