Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.4.23.16 (
HIV-1 protease
)
2,107
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The reversible phosphorylation of the alpha-subunit of eukaryotic translation initiation factor 2 (eIF2alpha) is a well-characterized mechanism of translational control in response to a wide variety of cellular stresses, including viral infection. Beside PKR, the eIF2alpha kinase
GCN2
participates in the cellular response against viral infection by RNA viruses with central nervous system tropism. PKR has also been involved in the antiviral response against HIV-1, although this antiviral effect is very limited due to the distinct mechanisms evolved by the virus to counteract PKR action. Here we report that infection of human cells with HIV-1 conveys the proteolytic cleavage of
GCN2
and that purified HIV-1 and HIV-2 proteases produce direct proteolysis of
GCN2
in vitro, abrogating the activation of
GCN2
by HIV-1 RNA. Transfection of distinct cell lines with a plasmid encoding an HIV-1 cDNA clone competent for a single round of replication resulted in the activation of
GCN2
and the subsequent eIF2alpha phosphorylation. Moreover, transfection of
GCN2
knockout cells or cells with low levels of phosphorylated eIF2alpha with the same HIV-1 cDNA clone resulted in a marked increase of HIV-1 protein synthesis. Also, the over-expression of
GCN2
in cells led to a diminished viral protein synthesis. These findings suggest that viral RNA produced during HIV-1 infection activates
GCN2
leading to inhibition of viral RNA translation, and that
HIV-1 protease
cleaves
GCN2
to overcome its antiviral effect.
...
PMID:GCN2 has inhibitory effect on human immunodeficiency virus-1 protein synthesis and is cleaved upon viral infection. 2311 64
