Infected cell protein 34.5

Neurovirulence factor ICP34.5
Identifiers
OrganismHuman alphaherpesvirus 1 strain 17
SymbolICP34.5
UniProtP36313
Search for
StructuresSwiss-model
DomainsInterPro

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 (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 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]

  1. ^ a b Agarwalla PK, Aghi MK (2012). "Oncolytic herpes simplex virus engineering and preparation". Oncolytic Viruses. Methods in Molecular Biology. Vol. 797. pp. 1–19. doi:10.1007/978-1-61779-340-0_1. ISBN 978-1-61779-339-4. 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. S2CID 11464646.