Time-course induction of apoptosis by wild-type and attenuated strains of rubella virus

Cooray, Samantha; Best, Jennifer M.

doi:10.1099/vir.0.18785-0

Cited by 13 publications

(11 citation statements)

References 25 publications

(27 reference statements)

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“…RV-induced apoptotic signaling has been reported to occur between 12-24 hours p.i., with peak caspase activity occurring around 72 hours p.i. at a multiplicity of infection (MOI) of 3 PFU/cell [6]. Fig.…”

Section: Inhibition Of Pi3k Results In An Increase In the Speed And Mmentioning

confidence: 99%

“…GSK-3β and c-myc were also detectable in the mock-infected cells at 96 hours p.i. [6,8,9]. The XTT assay was used to examine the effect of RV infection and LY29002 and U0126 treatment on cellular metabolism over time.…”

Section: Phosphorylation Of Akt Erk1/2 and Their Downstream Targets mentioning

confidence: 99%

“…The cellular mechanisms activated by RV, which lead to the disruption of organogenesis, are not fully understood. However, in permissive cell cultures, the cytopathic effect (CPE) of RV has been shown to be due to caspase-dependent apoptosis [6][7][8][9][10][11][12]. Apoptosis is a key component of developmental processes in mammals, which functions to delete vestigial structures, control cell number and remodel tissues and organs [13].…”

Section: Introductionmentioning

confidence: 99%

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The involvement of survival signaling pathways in rubella-virus induced apoptosis

Cooray

Jin²,

Best

2005

Virol J

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Rubella virus (RV) causes severe congenital defects when acquired during the first trimester of pregnancy. RV cytopathic effect has been shown to be due to caspase-dependent apoptosis in a number of susceptible cell lines, and it has been suggested that this apoptotic induction could be a causal factor in the development of such defects. Often the outcome of apoptotic stimuli is dependent on apoptotic, proliferative and survival signaling mechanisms in the cell. Therefore we investigated the role of phosphoinositide 3-kinase (PI3K)-Akt survival signaling and Ras-Raf-MEK-ERK proliferative signaling during RV-induced apoptosis in RK13 cells. Increasing levels of phosphorylated ERK, Akt and GSK3β were detected from 24-96 hours post-infection, concomitant with RV-induced apoptotic signals. Inhibition of PI3K-Akt signaling reduced cell viability, and increased the speed and magnitude of RV-induced apoptosis, suggesting that this pathway contributes to cell survival during RV infection. In contrast, inhibition of the Ras-Raf-MEK-ERK pathway impaired RV replication and growth and reduced RV-induced apoptosis, suggesting that the normal cellular growth is required for efficient virus production.

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Section: Inhibition Of Pi3k Results In An Increase In the Speed And Mmentioning

confidence: 99%

Section: Phosphorylation Of Akt Erk1/2 and Their Downstream Targets mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The involvement of survival signaling pathways in rubella-virus induced apoptosis

Cooray

Jin²,

Best

2005

Virol J

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“…Transfected cells were selected using anti-CD20-coated magnetic beads on a magnetic-activated cell sorter (MACS) column 24 h post-transfection. Cells were replated in fresh medium, incubated for a further 24 h at 37 °C and then stimulated with 1 μM ST for 4 h. Cell lysates were tested for caspase 3/7 activity and caspase 3/PARP cleavage using antibodies that detected the cleaved 17 (p17) and 89 kDa (p89) fragments, respectively, as described previously (Cooray et al , 2003). Equivalent loading was verified by blotting for α -tubulin (Upstate).…”

Section: Methodsmentioning

confidence: 99%

Functional and structural studies of the vaccinia virus virulence factor N1 reveal a Bcl-2-like anti-apoptotic protein

Cooray

Bahar

Abrescia

et al. 2007

Journal of General Virology

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158

223

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Vaccinia virus (VACV) encodes many immunomodulatory proteins, including inhibitors of apoptosis and modulators of innate immune signalling. VACV protein N1 is an intracellular homodimer that contributes to virus virulence and was reported to inhibit nuclear factor (NF)-κB signalling. However, analysis of NF-κB signalling in cells infected with recombinant viruses with or without the N1L gene showed no difference in NF-κB-dependent gene expression. Given that N1 promotes virus virulence, other possible functions of N1 were investigated and this revealed that N1 is an inhibitor of apoptosis in cells transfected with the N1L gene and in the context of VACV infection. In support of this finding virally expressed N1 co-precipitated with endogenous pro-apoptotic Bcl-2 proteins Bid, Bad and Bax as well as with Bad and Bax expressed by transfection. In addition, the crystal structure of N1 was solved to 2.9 Å resolution (0.29 nm). Remarkably, although N1 shows no sequence similarity to cellular proteins, its three-dimensional structure closely resembles Bcl-xL and other members of the Bcl-2 protein family. The structure also reveals that N1 has a constitutively open surface groove similar to the grooves of other anti-apoptotic Bcl-2 proteins, which bind the BH3 motifs of pro-apoptotic Bcl-2 family members. Molecular modelling of BH3 peptides into the N1 surface groove, together with analysis of their physico-chemical properties, suggests a mechanism for the specificity of peptide recognition. This study illustrates the importance of the evolutionary conservation of structure, rather than sequence, in protein function and reveals a novel anti-apoptotic protein from orthopoxviruses.

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“…The induction of apoptosis through RV infection is caspase dependent [164,165]. Apoptosis still occurs in the presence of caspase inhibitors though, indicating an alternative mechanism of induction of apoptosis.…”

Section: Togaviridae Rubella Virus (Rv)mentioning

confidence: 99%

Viral Manipulation of Cell Death

Zakeri

McLean

Rück³

et al. 2008

CPD

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Elucidation of the mechanisms behind cell death has brought with it an appreciation for viral strategies that target these pathways as a means to promote viral propagation while avoiding or slowing the host immune response. Several redundant anti-viral pathways have evolved in eukaryotic cells that are designed to minimize the damage due to viral infection while quickly clearing the invading pathogen. Cell death is a commonly employed immune defense against viral infection, and many viruses potently induce or suppress cell death during infection. The past decade has seen an incredible increase in our understanding of how cell death assists in host immune response, as well as how viruses have evolved to hijack or disengage these systems. By targeting components of host cell death pathways, viruses have developed the ability to control host survival and death, ensuring efficient propagation while inactivating or avoiding the immune system consequences of infection. This review focuses on the most recent and important advances in our understanding of how a wide range of viruses manipulate the survival and death of their hosts.

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Time-course induction of apoptosis by wild-type and attenuated strains of rubella virus

Cited by 13 publications

References 25 publications

The involvement of survival signaling pathways in rubella-virus induced apoptosis

The involvement of survival signaling pathways in rubella-virus induced apoptosis

Functional and structural studies of the vaccinia virus virulence factor N1 reveal a Bcl-2-like anti-apoptotic protein

Viral Manipulation of Cell Death

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