Infected cell protein 34.5

Infected cell protein 34.5 (ICP-34.5, ICP34.5, or GADD34) is a protein expressed by the ɣ34.5 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 (InterPro: IPR019523) with protein phosphatase 1 subunit 15A/B.

Neurovirulence factor ICP34.5
Identifiers
OrganismHuman alphaherpesvirus 1 strain 17
SymbolICP34.5
UniProtP36313

When a cell is infected with a virus, protein kinase R is activated by the virus' double-stranded RNA,. 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 ɣ34.5 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]

See also


References
  1. Agarwalla PK, Aghi MK (2012). "Oncolytic herpes simplex virus engineering and preparation". Methods in Molecular Biology. 797: 1–19. doi:10.1007/978-1-61779-340-0_1. PMID 21948465.
  2. Liu BL, Robinson M, Han ZQ, Branston RH, English C, Reay P, et al. (February 2003). "ICP34.5 deleted herpes simplex virus with enhanced oncolytic, immune stimulating, and anti-tumour properties". Gene Therapy. 10 (4): 292–303. doi:10.1038/sj.gt.3301885. PMID 12595888.
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