Several Alphaherpesviruses Interact Similarly with the NF-κB Pathway and Suppress NF-κB-Dependent Gene Expression

Alphaherpesvirus infection is associated with attenuation of different aspects of the host innate immune response that is elicited to confine primary infections at the mucosal epithelia. Here, we report that infection of epithelial cells with several alphaherpesviruses of different species, including herpes simplex virus 1 and 2 (HSV-1 and HSV-2), feline alphaherpesvirus 1 (FHV-1), and bovine alphaherpesvirus 1 (BoHV-1) results in the inactivation of the responses driven by the nuclear factor kappa B (NF-?B) pathway, considered a pillar of the innate immune response. The mode to interact with and circumvent NF-?B-driven responses in infected epithelial cells is seemingly conserved in human, feline, and porcine alphaherpesviruses, consisting of a persistent activation of the NF-?B cascade but a potent repression of NF-?B-dependent transcription activity, which relies on replication of viral genomes. However, BoHV-1 apparently deviates from the other investigated members of the taxon in this respect, as BoHV-1-infected epithelial cells do not display the persistent NF-?B activation observed for the other alphaherpesviruses. In conclusion, this study suggests that inhibition of NF-?B transcription activity is a strategy used by several alphaherpesviruses to prevent NF-?B-driven responses in infected epithelial cells.

Automated summary

This study reveals that infection of epithelial cells by different species of alphaherpesviruses results in the inactivation of the nuclear factor kappa B (NF-?B) pathway, which weakens the host innate immune response. The mode of interaction with NF-?B-driven responses seems to be conserved in human, feline, and porcine alphaherpesviruses, but there are some differences in bovine alphaherpesvirus. Overall, the study suggests that multiple alphaherpesviruses use the strategy of inhibiting NF-?B transcription activity to prevent NF-?B-driven responses in infected epithelial cells.