HSV-1, as well as beta-and gammaherpesviruses, are capable of stimulating the NF-kB pathway in a bi-phasic manner, with our data supporting that an early, transient induction is reliant on virions expressing gD [8] [32] [33] . Suppression of NF-kB activity is via negative feedback up-regulation of the inhibitor IkBa (nfkbia), which was also stimulated by the binding of entry-defective HSV-1 virions. The triggering of early NF-kB transcriptional activity was most likely through the coupling of gD on entry-defective virions to the TNF superfamily receptor HvEM [1] . In doing so, not only does the initial activation of this pathway allow for the subsequent sequestration of the NF-kB p65 subunit to the ICP0 promoter, but is crucial for immediate-early gene transcription and subsequent HSV-1 replication [8] . Intracellular signalling induced by soluble gD can protect against Fas-mediated apoptosis with inhibition of NF-kB signalling leading to a loss of this protection [6] . Infection with UV-inactivated virions also led to an increase in the expression of the anti-apoptotic protein c-IAP2 (birc3), which we have demonstrated to be up-regulated after inoculation with entry-defective virions containing gD. Additional studies have supported the anti-apoptotic role for NF-kB during HSV-1 infection yet there are conflicting data that demonstrate possible pro-apoptotic activity [34] [35] . This inconsistency may be due to differing cell types used in those studies. Primary human foreskin fibroblasts have been shown to be resistant to apoptosis after infection with recombinant HSV-1 that is unable to express ICP4 or ICP27 whereas infection with either virus has been shown to cause apoptosis in transformed cell lines [36] .