Signalling by secreted Type I IFNs occurs through the Jak/Stat pathway results in the expression of various ISGs; a response that is also triggered by virus entry [39] . Nevertheless, productive infection with HSV-1 can down-regulate the triggered ISG response, allowing viral replication to continue unhindered [40] . Despite our evidence that gD binding by entry-defective virions can induce IFN-a mRNA expression, independent of gD glycosylation status, these data also fit with published observations that binding by HSV-1 is insufficient to cause the up-regulation of interferon-stimulated genes [30] . The up-regulation of IFN-b, albeit it through a different mechanism, is suggestive of a previously unidentified role for gH in eliciting a change in host gene expression. An entry-defective HSV-1 mutant lacking gB that also contains an RGE rather than the integrin binding RGD motif of gH has been constructed and future studies may further elicit the role of gH in interferon stimulation.