Antagonism of Innate Immunity by Paramyxovirus Accessory Proteins

Chambers, Raychel; Takimoto, Toru

doi:10.3390/v1030574

Cited by 16 publications

(10 citation statements)

References 113 publications

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“…Viruses utilize a number of strategies for counteracting immune and apoptotic signals. Previous studies have demonstrated that paramyxoviruses can use the accessory proteins from the P/V/C gene to inhibit apoptosis [ 33 , 34 ]. The V protein of mumps virus is also known to block IFN expression [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

Proteomics informed by transcriptomics reveals Hendra virus sensitizes bat cells to TRAIL-mediated apoptosis

et al. 2014

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BackgroundBats are a major reservoir of emerging infectious viruses. Many of these viruses are highly pathogenic to humans however bats remain asymptomatic. The mechanism by which bats control viral replication is unknown. Here we utilize an integrated approach of proteomics informed by transcriptomics to compare the response of immortalized bat and human cells following infection with the highly pathogenic bat-borne Hendra virus (HeV).ResultsThe host response between the cell lines was significantly different at both the mRNA and protein levels. Human cells demonstrated minimal response eight hours post infection, followed by a global suppression of mRNA and protein abundance. Bat cells demonstrated a robust immune response eight hours post infection, which led to the up-regulation of apoptosis pathways, mediated through the tumor necrosis factor-related apoptosis inducing ligand (TRAIL). HeV sensitized bat cells to TRAIL-mediated apoptosis, by up-regulating death receptor transcripts. At 48 and 72 hours post infection, bat cells demonstrated a significant increase in apoptotic cell death.ConclusionsThis is the first study to comprehensively compare the response of bat and human cells to a highly pathogenic zoonotic virus. An early induction of innate immune processes followed by apoptosis of virally infected bat cells highlights the possible involvement of programmed cell death in the host response. Our study shows for the first time a side-by-side high-throughput analysis of a dangerous zoonotic virus in cell lines derived from humans and the natural bat host. This enables a way to search for divergent mechanisms at a molecular level that may influence host pathogenesis.Electronic supplementary materialThe online version of this article (doi:10.1186/s13059-014-0532-x) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Proteomics informed by transcriptomics reveals Hendra virus sensitizes bat cells to TRAIL-mediated apoptosis

et al. 2014

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“…The incapacity of RSV to fully inhibit SG formation, in contrast to MV and SeV, might reflect the lack of expression of the C protein from the RSV genome. In the context of SeV or MV infection, the C protein that results from the translation from an alternative overlapping open reading frame of the P gene [ 12 ], is mainly responsible for interference with SG formation [ 55 , 61 , 62 ]. In contrast to wt viruses, MV or SeV mutants deleted for the C protein expression are strong inducers of G3BP1-positive SG formation.…”

Section: Rsv Takes Advantage Of Cytoplasmic Sgs and Specific Ibsmentioning

confidence: 99%

Respiratory Syncytial Virus and Cellular Stress Responses: Impact on Replication and Physiopathology

Cervantes-Ortiz

Cuervo

2016

Viruses

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Human respiratory syncytial virus (RSV), a member of the Paramyxoviridae family, is a major cause of severe acute lower respiratory tract infection in infants, elderly and immunocompromised adults. Despite decades of research, a complete integrated picture of RSV-host interaction is still missing. Several cellular responses to stress are involved in the host-response to many virus infections. The endoplasmic reticulum stress induced by altered endoplasmic reticulum (ER) function leads to activation of the unfolded-protein response (UPR) to restore homeostasis. Formation of cytoplasmic stress granules containing translationally stalled mRNAs is a means to control protein translation. Production of reactive oxygen species is balanced by an antioxidant response to prevent oxidative stress and the resulting damages. In recent years, ongoing research has started to unveil specific regulatory interactions of RSV with these host cellular stress responses. Here, we discuss the latest findings regarding the mechanisms evolved by RSV to induce, subvert or manipulate the ER stress, the stress granule and oxidative stress responses. We summarize the evidence linking these stress responses with the regulation of RSV replication and the associated pathogenesis.

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“…As shown in Figure 6A , the ErbB3 promoter activity was increased in HBx-expressing cells in a dose-dependent manner, indicating that HBx transcriptionally increased ErbB3 gene expression. HBx has been reported to activate various transcription factors such as AP-1, NF-κB, and CREB [ 51 – 53 ]. By using JASPAR database, the putative transcription factors binding to ErbB3 promoter were predicted (Figure 6B ), and among them Sp-1, NF-κB, AP1, E2F1, and HNF4α have been reported to be activated in response to HBx expression [ 54 – 58 ].…”

Section: Resultsmentioning

confidence: 99%

HBx sensitizes hepatocellular carcinoma cells to lapatinib by up-regulating ErbB3

Chen

Yen

et al. 2015

Oncotarget

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Poor prognosis of hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) involves HBV X protein (HBx)-induced tumor progression. HBx also contributes to chemo-resistance via inducing the expressions of anti-apoptosis and multiple drug resistance genes. However, the impact of HBx expression on the therapeutic efficacy of various receptor tyrosine kinase inhibitors remains unknown. In this study, our data showed that HBx overexpression did not alter the cellular sensitivity of HCC cell lines to sorafenib but unexpectedly enhanced the cell death induced by EGFR family inhibitors, including gefitinib, erlotinib, and lapatinib due to ErbB3 up-regulation. Mechanistically, HBx transcriptionally up-regulates ErbB3 expression in a NF-κB dependent manner. In addition, HBx also physically interacts with ErbB2 and ErbB3 proteins and enhances the formation of ErbB2/ErbB3 heterodimeric complex. The cell viability of HBx-overexpressing cells was decreased by silencing ErbB3 expression, further revealing the pivotal role of ErbB3 in HBx-mediated cell survival. Our data suggest that HBx shifts the oncogenic addiction of HCC cells to ErbB2/ErbB3 signaling pathway via inducing ErbB3 expression and thereby enhances their sensitivity to EGFR/ErbB2 inhibitors.

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Antagonism of Innate Immunity by Paramyxovirus Accessory Proteins

Cited by 16 publications

References 113 publications

Proteomics informed by transcriptomics reveals Hendra virus sensitizes bat cells to TRAIL-mediated apoptosis

Proteomics informed by transcriptomics reveals Hendra virus sensitizes bat cells to TRAIL-mediated apoptosis

Respiratory Syncytial Virus and Cellular Stress Responses: Impact on Replication and Physiopathology

HBx sensitizes hepatocellular carcinoma cells to lapatinib by up-regulating ErbB3

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