Infected cell protein 34.5
| Neurovirulence factor ICP34.5 | |||||||
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| Organism | |||||||
| Symbol | ICP34.5 | ||||||
| UniProt | P36313 | ||||||
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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.
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
- ^ a b 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.
- ^ 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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