Sendai Virus Targets Inflammatory Responses, as Well as the Interferon-Induced Antiviral State, in a Multifaceted Manner

Strahle, Laura Eve; Garcin, Dominique; Mercier, Philippe Le; Schlaak, Joerg F.; Kolakofsky, Daniel

doi:10.1128/jvi.77.14.7903-7913.2003

Cited by 32 publications

(32 citation statements)

References 70 publications

(84 reference statements)

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“…Most of the previous studies of the function of paramyxovirus C accessory proteins addressed the analysis of the modulation of type I IFN induction. Sendai virus (SeV) mutants unable to express either the C gene or the V gene induced elevated levels of host type I IFN production, and the product of the SeV C open reading frame can directly limit type I IFN induction (35,54,55). Measles virus that cannot express the C protein also induces more type I IFN than the wild-type virus (42).…”

Section: Discussionmentioning

confidence: 99%

Nonstructural Nipah Virus C Protein Regulates both the Early Host Proinflammatory Response and Viral Virulence

Mathieu

Guillaume

Volchkova

et al. 2012

J Virol

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Nipah virus (NiV) is a highly pathogenic, negative-strand RNA paramyxovirus that has recently emerged from flying foxes to cause serious human disease. We have analyzed the role of the nonstructural NiV C protein in viral immunopathogenesis using recombinant virus lacking the expression of NiV C (NiVΔC). While wild-type NiV was highly pathogenic in the hamster animal model, NiVΔC was strongly attenuated. Replication of NiVΔC was followed by the production of NiV-specific antibodies and associated with higher recruitment of inflammatory cells and less intensive histopathological lesions in different organs than in wild-type-NiV-infected animals. To analyze the molecular basis of NiVΔC attenuation, we studied early changes in gene expression in infected primary human endothelial cells, a major cellular target of NiV infection. The transcriptomic approach revealed the striking difference between wild-type and mutant NiV in the expression of genes involved in immunity, with the particularly interesting differential patterns of proinflammatory cytokines. Compared to wild-type virus, NiVΔC induced increased expression of interleukin 1 beta (IL-1β), IL-8, CXCL2, CXCL3, CXCL6, CCL20, and beta interferon. Furthermore, the expression of NiV C in stably transfected cells decreased the production of the same panel of cytokines, revealing a role of the C protein in the regulation of cytokine balance. Together, these results suggest that NiV C regulates expression of proinflammatory cytokines, therefore providing a signal responsible for the coordination of leukocyte recruitment and the chemokine-induced immune response and controlling the lethal outcome of the infection.

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Section: Discussionmentioning

confidence: 99%

Nonstructural Nipah Virus C Protein Regulates both the Early Host Proinflammatory Response and Viral Virulence

Mathieu

Guillaume

Volchkova

et al. 2012

J Virol

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“…rSeV-GFP(ϩ), which expresses green fluorescent protein (GFP) from a transgene between the M and F genes, and rSeV-E3L 100 -190 , which expresses E3L 100 -190 from a similarly located transgene, were prepared as previously described (23). DI-H4 stocks were described previously (24).…”

Section: Methodsmentioning

confidence: 99%

The Double-stranded RNA Binding Domain of the Vaccinia Virus E3L Protein Inhibits Both RNA- and DNA-induced Activation of Interferon β

Marq

Hausmann

Luban

et al. 2009

Journal of Biological Chemistry

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Vaccinia virus, a large DNA virus that replicates in the cytoplasm, expresses its E3L protein to inhibit the cellular innate immune response and apoptosis. E3L is a bifunctional protein that contains an N-terminal DNA binding domain (BD) and a C-terminal double-stranded RNA (dsRNA)-BD (residues 100 -190), both of which contribute to viral pathogenesis by blocking the activation of cellular genes that respond to the viral infection. We report that expression of the dsRNA-BD alone inhibits not only the dsRNA-induced activation of interferon ␤ (IFN␤) but also that of 5-triphosphate single-stranded RNA and DNAinduced IFN␤ activation even though E3L 100 -190 does not bind the latter two pathogen-associated molecular patterns. This inhibition occurs in both human HeLa and A549 cells, where RIG-I appears to be required for dsDNA-induced IFN␤ activation. Unexpectedly, the two residues most important for dsRNA binding are also critical for this domain's ability to inhibit all three nucleic acid-induced cellular responses.

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“…QPCR analysis of MyD88 and IFN-␤ were performed by using SYBR green I dye. Primer sequences for IFN-␤ and MyD88 have been previously described (43,49). Quantifications of the genes of interest were normalized to GAPDH (glyceraldehyde-3-phosphate dehydrogenase) and expressed as the factors of increase over the negative control for each treatment at each time point.…”

Section: Methodsmentioning

confidence: 99%

Differential Role for TLR3 in Respiratory Syncytial Virus-Induced Chemokine Expression

Rudd

Burstein

Duckett

et al. 2005

J Virol

249

203

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Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection in young infantsworldwide. Previous studies have reported that the induction of interleukin-8/CXCL8 and RANTES/CCL5 correlates with disease severity in humans. The production of these chemokines is elicited by viral replication and is NF-B dependent. RSV, a negative-sense single-stranded RNA virus, requires full-length positive-sense RNA for synthesis of new viral RNA. The aim of our studies was to investigate whether active viral replication by RSV could evoke chemokine production through TLR3-mediated signaling pathways. In TLR3-transfected HEK 293 cells, live RSV preferentially activated chemokines in both a time-and dose-dependent manner compared to vector controls. RSV was also shown to upregulate TLR3 in human lung fibroblasts and epithelial cells (MRC-5 and A549). Targeting the expression of TLR3 with small interfering RNA decreased synthesis of IP-10/CXCL10 and CCL5 but did not significantly reduce levels of CXCL8. Blocking the expression of the adapter protein MyD88 established a role for MyD88 in CXCL8 production, whereas CCL5 synthesis was found to be MyD88 independent. Production of CCL5 by RSV was induced directly through TLR3 signaling pathways and did not require interferon (IFN) signaling through the IFN-␣/␤ receptor. TLR3 did not affect viral replication, since equivalent viral loads were recovered from RSV-infected cells despite altered TLR3 expression. Taken together, our studies indicate that TLR3 mediates inflammatory cytokine and chemokine production in RSV-infected epithelial cells.

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Sendai Virus Targets Inflammatory Responses, as Well as the Interferon-Induced Antiviral State, in a Multifaceted Manner

Cited by 32 publications

References 70 publications

Nonstructural Nipah Virus C Protein Regulates both the Early Host Proinflammatory Response and Viral Virulence

Nonstructural Nipah Virus C Protein Regulates both the Early Host Proinflammatory Response and Viral Virulence

The Double-stranded RNA Binding Domain of the Vaccinia Virus E3L Protein Inhibits Both RNA- and DNA-induced Activation of Interferon β

Differential Role for TLR3 in Respiratory Syncytial Virus-Induced Chemokine Expression

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