The neurovirulence factor ICP34.5 or also "Infected Cell Protein 34.5" is a protein that is encoded by the ɣ34.5 gene in viruses (e.g. in the herpes simplex virus). It is likely that the neurovirulence factor ICP34.5 was evolved by viruses to overcome a cell's defenses. ICP34.5 activates protein phosphatase-1A, which dephosphorylates eIF-2A, allowing translation to resume. A herpes virus in which the neurovirulence factor ICP34.5 is inactivated causes tumor-specific cell lysis.
Neurovirulence factor ICP34.5
DefinitionThis section has been translated automatically.
General informationThis section has been translated automatically.
When a cell is infected with a virus, protein kinase R is activated by the double-stranded RNA of the virus. Protein kinase R then phosphorylates a protein called eukaryotic initiation factor-2A (eIF-2A), which inactivates eIF-2A. EIF-2A is required for translation. By turning off eIF-2A, the cell prevents the virus from using the cell's protein-making machinery (Liu BL et al (2003).
PathophysiologyThis section has been translated automatically.
The neurovirulence factor ICP34.5 was developed by viruses to overcome the cell's defenses. ICP34.5 activates protein phosphatase-1A, which dephosphorylates eIF-2A, allowing translation to resume. A herpes virus in which the neurovirulence factor ICP34.5 is inactivated causes tumor-specific cell lysis.
Clinical pictureThis section has been translated automatically.
The importance of the neurovirulence factor ICP34.5 is illustrated by the following example: by deleting the viral herpes neurovirulence genes, an attenuated biological "vaccine" can be developed, which has simultaneously been enhanced in its immunogenicity by deleting the viral ICP47 gene and further gene modulations. The viral agent is designed to detect and replicate in e.g. melanoma cells. Targeted infection of tumor cells with mass replication of the virus leads to destruction of the infected tumor cell. The viral oncolysis induced in this way results in a systemically relevant, anti-tumour immune response, which sustainably and specifically attacks other tumour cell nests located in the body (Bhandaru M et al. 2019).
LiteratureThis section has been translated automatically.
- Bhandaru M et al (2019) Monoclonal Antibodies for the Treatment of Melanoma: Present and Future Strategies. Methods Mol Biol 1904:83-108.
- Liu BL et al. (2003) ICP34.5 deleted herpes simplex virus with enhanced oncolytic, immune stimulating, and anti-tumour properties. Gene Ther 10:292-303
- Tang S et al (2009) Novel less-abundant viral microRNAs encoded by herpes simplex virus 2 latency-associated transcript and their roles in regulating ICP34.5 and ICP0 mRNAs. J Virol 83:1433-1442.