Infected cell protein 34.5 (ICP34.5) (ICP34.5)

ICP34.5 is a 248-amino-acid neurovirulence factor protein produced by herpes simplex virus types 1 and 2 that serves as a critical determinant of viral pathogenesis, particularly in neuronal infections. The protein functions through multiple mechanisms to facilitate viral replication and evade host immune responses, including acting as a molecular scaffold that bridges protein phosphatase 1 and the translation initiation factor eIF2α to restore viral protein synthesis following infection-induced phosphorylation. Additionally, ICP34.5 inhibits autophagy through beclin1 binding, facilitates viral nuclear egress, and modulates mitochondrial dynamics in infected neurons. The deletion or mutation of ICP34.5 dramatically reduces viral virulence in the brain (by up to 10^6-fold) and impairs the establishment of latency, making it a significant target for antiviral therapeutic development. While not a human cellular target, understanding ICP34.5 function is crucial for developing antivirals and attenuated live vaccine candidates against herpes simplex virus infections.

Other names

Neurovirulence factor ICP34.5Viral protein ICP34.5γ1 34.5 gene productInfected-cell protein 34.5

ICP34.5 functions as a molecular bridge or scaffold protein that brings PP1 and eIF2α into proximity, enabling PP1-mediated dephosphorylation of eIF2α. This prevents the translation shutdown that normally occurs in response to viral infection.