| Neurovirulence factor ICP34.5 | |
| Symbol: | ICP34.5 |
| Uniprot: | P36313 |
| Organism: | Human alphaherpesvirus 1 strain 17 |
Infected cell protein 34.5 (ICP-34.5, ICP34.5) is a protein expressed by the γ34.5 gene in viruses such as herpes simplex virus; it blocks a cellular stress response to viral infection.[1] It shares the C-terminal regulatory domain with protein phosphatase 1 subunit 15A/B.
When a cell is infected with a virus, protein kinase R is activated by the virus' double-stranded DNA,. Protein kinase R then phosphorylates a protein called eukaryotic initiation factor-2A (eIF-2A), which inactivates eIF-2A. EIF-2A is required for translation so by shutting down eIF-2A, the cell prevents the virus from hijacking its own protein-making machinery. Viruses in turn evolved ICP34.5 to defeat the defense; it activates protein phosphatase-1A which dephosphorylates eIF-2A, allowing translation to occur again. A herpesvirus lacking the γ34.5 gene will not be able to replicate in normal cells because it cannot make proteins.[1]
The ICP34.5 deletion is useful for the construction of oncolytic herpes viruses, as cancer cells do not restrict replication as strongly.[2]