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PMID:23115297
| Citation |
Urbanowski, MD and Hobman, TC (2013) The West Nile virus capsid protein blocks apoptosis through a phosphatidylinositol 3-kinase-dependent mechanism. J. Virol. 87:872-81 |
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| Abstract |
West Nile virus (WNV) is a mosquito-transmitted pathogen that can cause serious disease in humans. Our laboratories are focused on understanding how interactions between WNV proteins and host cells contribute to virus replication and pathogenesis. WNV replication is relatively slow, and on the basis of earlier studies, the virus appears to activate survival pathways that delay host cell death during virus replication. The WNV capsid is the first viral protein produced in infected cells; however, its role in virus assembly is not required until after replication of the genomic RNA. Accordingly, from a temporal perspective, it is perfectly suited to block host cell apoptosis during virus replication. In the present study, we provide evidence that the WNV capsid protein blocks apoptosis through a phosphatidylinositol (PI) 3-kinase-dependent pathway. Specifically, expression of this protein in the absence of other viral proteins increases the levels of phosphorylated Akt, a prosurvival kinase that blocks apoptosis through multiple mechanisms. Treatment of cells with the PI 3-kinase inhibitor LY294002 abrogates the protective effects of the WNV capsid protein. |
| Links |
PubMed Online version:10.1128/JVI.02030-12 |
| Keywords |
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Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
| GO:0019050: suppression by virus of host apoptotic process |
ECO:0000314: |
P |
As is the case with many RNA viruses, infection of mammalian cells with West Nile Virus has been reported to cause apoptosis. Replication of WNV and other flaviviruses is relatively slow, and therefore, it is not seemingly beneficial to the virus if the first viral protein produced in an infected cell induces programmed cell death. In contrast, during the early stages of flavivirus infection, apoptosis appears to be inhibited by a process that involves activation of the prosurvival kinase Akt. Recent studies revealed that antiapoptotic/survival signaling is activated shortly after flavivirus infection. This signaling process involves the kinase Akt, which is activated by PI3K-dependent phosphorylation on serine 473. As seen in figure 7, inhibition of PI3 kinase abrogates protection by WNV capsid protein. This was done when A549 cells were transduced with lentiviruses encoding WNV capsid protein or AcGFP alone, before challenge with anti-Fas with or without addition of LY294002. |
complete | ||||
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involved_in |
GO:0019050: suppression by virus of host apoptotic process |
ECO:0000314: direct assay evidence used in manual assertion |
P |
Seeded From UniProt |
complete | |||
See also
References
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