Infected cell protein 34.5 (ICP-34.5, ICP34.5, or GADD34) is a protein expressed by the γ34.5 gene in viruses such as
herpes simplex virus
Herpes simplex virus 1 and 2 (HSV-1 and HSV-2), also known by their taxonomical names ''Human alphaherpesvirus 1'' and '' Human alphaherpesvirus 2'', are two members of the human ''Herpesviridae'' family, a set of viruses that produce viral inf ...
; it blocks a
cellular stress response Cellular stress response is the wide range of molecular changes that cells undergo in response to environmental stressors, including extremes of temperature, exposure to toxins, and mechanical damage. Cellular stress responses can also be caused b ...
to viral infection.
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
Protein kinase RNA-activated also known as protein kinase R (PKR), interferon-induced, double-stranded RNA-activated protein kinase, or eukaryotic translation initiation factor 2-alpha kinase 2 (EIF2AK2) is an enzyme that in humans is encoded by t ...
is activated by the virus'
double-stranded DNA,. Protein kinase R then
phosphorylates
In chemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology and could be driven by natural selection. Text was copied from this source, whi ...
a protein called
eukaryotic initiation factor-2A (eIF-2A), which inactivates eIF-2A. EIF-2A is required for
translation
Translation is the communication of the Meaning (linguistic), meaning of a #Source and target languages, source-language text by means of an Dynamic and formal equivalence, equivalent #Source and target languages, target-language text. The ...
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.
[
The ICP34.5 deletion is useful for the construction of ]oncolytic herpes virus
Many variants of herpes simplex virus have been considered for viral therapy of cancer; the early development of these was thoroughly reviewed in the journal ''Cancer Gene Therapy'' in 2002. This page describes (in the order of development) the ...
es, as cancer cells do not restrict replication as strongly.
See also
* Viral nonstructural protein In virology, a nonstructural protein is a protein encoded by a virus but that is not part of the viral particle. They typically include the various enzymes and transcription factors the virus uses to replicate itself, such as a viral protease ( 3CL ...
References
Viral nonstructural proteins
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