Regulation of type I-interferon responses in the human epidermal melanocyte cell line SKMEL infected by the Ross River alphavirus

Assi, Mohamad; Thon-Hon, Vincent G.; Jaffar‐Bandjee, Marie‐Christine; Martinez, Audrey; Gasque, Philippe

doi:10.1016/j.cyto.2015.07.003

Cited by 6 publications

(5 citation statements)

References 15 publications

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“…Our analyses revealed that compared to SeV infection, induction of type I IFN ( ifnb ) transcripts in MAYV-infected cells was dramatically suppressed and significantly delayed. These findings are consistent with earlier studies on other alphaviruses such as SINV, CHIKV, Ross River virus, Venezuelan Equine Encephalitis virus, and Eastern Equine Encephalitis virus [ 28 , 38 ]. Similarly, production of type III IFN transcripts was inhibited, and secretion of IFN-β was completely abrogated by MAYV infection.…”

Section: Discussionsupporting

confidence: 93%

“…In this study, we investigated how MAYV infection affects the IFN induction pathway. Similar to what has been reported for other alphaviruses [ 28 , 29 , 38 ], MAYV infection efficiently suppressed induction and secretion of IFN. Mapping studies indicated that nsP2 of MAYV blocks a step in the IFN induction pathway that is downstream of IRF3 phosphorylation.…”

Section: Introductionsupporting

confidence: 86%

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Mayaro Virus Non-Structural Protein 2 Circumvents the Induction of Interferon in Part by Depleting Host Transcription Initiation Factor IIE Subunit 2

Ishida

Cole

López-Orozco

et al. 2021

Cells

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Mayaro virus (MAYV) is an emerging mosquito-transmitted virus that belongs to the genus Alphavirus within the family Togaviridae. Humans infected with MAYV often develop chronic and debilitating arthralgia and myalgia. The virus is primarily maintained via a sylvatic cycle, but it has the potential to adapt to urban settings, which could lead to large outbreaks. The interferon (IFN) system is a critical antiviral response that limits replication and pathogenesis of many different RNA viruses, including alphaviruses. Here, we investigated how MAYV infection affects the induction phase of the IFN response. Production of type I and III IFNs was efficiently suppressed during MAYV infection, and mapping revealed that expression of the viral non-structural protein 2 (nsP2) was sufficient for this process. Interactome analysis showed that nsP2 interacts with DNA-directed RNA polymerase II subunit A (Rpb1) and transcription initiation factor IIE subunit 2 (TFIIE2), which are host proteins required for RNA polymerase II-mediated transcription. Levels of these host proteins were reduced by nsP2 expression and during infection by MAYV and related alphaviruses, suggesting that nsP2-mediated inhibition of host cell transcription is an important aspect of how some alphaviruses block IFN induction. The findings from this study may prove useful in design of vaccines and antivirals, which are currently not available for protection against MAYV and infection by other alphaviruses.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionsupporting

confidence: 86%

Mayaro Virus Non-Structural Protein 2 Circumvents the Induction of Interferon in Part by Depleting Host Transcription Initiation Factor IIE Subunit 2

Ishida

Cole

López-Orozco

et al. 2021

Cells

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“…For this study, HEK293T cells were selected for their high sensitivity to the viral cytopathic effect, in contrast to the resistant skin cell lines [ 42 ]. In addition, we used a representative RRV strain to provide a fast and representative evaluation of essential oils against the alphaviruses family.…”

Section: Discussionmentioning

confidence: 99%

In vitro comparison of three common essential oils mosquito repellents as inhibitors of the Ross River virus

et al. 2018

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BackgroundThe essential oils of Cymbopogon citratus (CC), Pelargonium graveolens (PG) and Vetiveria zizanioides (VZ) are commonly used topically to prevent mosquito bites and thus the risk of infection by their vectored pathogens such as arboviruses. However, since mosquito bites are not fully prevented, the effect of these products on the level of viral infection remains unknown.ObjectivesTo evaluate in vitro the essentials oils from Reunion Island against one archetypal arbovirus, the Ross River virus (RRV), and investigate the viral cycle step that was impaired by these oils.MethodsThe essential oils were extracted by hydrodistillation and analyzed by a combination of GC-FID and GC×GC-TOF MS techniques. In vitro studies were performed on HEK293T cells to determine their cytotoxicity, their cytoprotective and virucidal capacities on RRV-T48 strain, and the level of their inhibitory effect on the viral replication and residual infectivity prior, during or following viral adsorption using the reporter virus RRV-renLuc.ResultsEach essential oil was characterized by an accurate quantification of their terpenoid content. PG yielded the least-toxic extract (CC50 > 1000 μg.mL-1). For the RRV-T48 strain, the monoterpene-rich CC and PG essential oils reduced the cytopathic effect but did not display virucidal activity. The time-of-addition assay using the gene reporter RRV-renLuc showed that the CC and PG essential oils significantly reduced viral replication and infectivity when applied prior, during and early after viral adsorption. Overall, no significant effect was observed for the low monoterpene-containing VZ essential oil.ConclusionThe inhibitory profiles of the three essential oils suggest the high value of the monoterpene-rich essential oils from CC and PG against RRV infection. Combined with their repellent activity, the antiviral activity of the essential oils of CC and PG may provide a new option to control arboviral infection.

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“…[ 4 ] Activation of NF‐κB and type I IFN pathways of MyDDosome and MAVSome leads to the nuclear translocation of the NF‐κB complex and interferon regulatory factor 3/7 (IRF3/IRF7) to induce the expressions of tumor necrosis factor‐α (TNF‐α), interleukin‐6 (IL‐6), and IFNs. Subsequent binding of IFNs to IFNAR [ 5 ] and IL‐6 to IL‐6R‐gp130 activate the STAT1/3 pathway [ 6 ] and the expression of IFN‐stimulated genes and proinflammatory cytokines, ultimately mounting a robust immune response that could be beneficial for pathogen defense. [ 7 ] Nevertheless, this host defensive reaction could also cause detrimental tissue injury or severe respiratory syndrome as seen in COVID‐19 patients infected with SARS‐CoV‐2.…”

Section: Introductionmentioning

confidence: 99%

Engineering Supramolecular Organizing Centers for Optogenetic Control of Innate Immune Responses

Tan

Zhou

2020

Advanced Biology

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Activation of NF-κB and type I IFN pathways of MyDDosome and MAVSome leads to the nuclear translocation of the NF-κB complex and interferon regulatory factor 3/7 (IRF3/IRF7) to induce the expressions of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IFNs. Subsequent binding of IFNs to IFNAR [5] and IL-6 to IL-6R-gp130 activate the STAT1/3 pathway [6] and the expression of IFN-stimulated genes and proinflammatory cytokines, ultimately mounting a robust immune response that could be beneficial for pathogen defense. [7] Nevertheless, this host defensive reaction could also cause detrimental tissue injury or severe respiratory syndrome as seen in COVID-19 patients infected with SARS-CoV-2. [8] For example, IFNs stimulate the expression of SARS-CoV-2 entry receptor ACE2 (angiotensin-converting enzyme 2) to favor viral infection and IL-6-induced severe respiratory syndrome. [9,10] The association of ligand with TLR triggers the recruitment of TLR-specific Toll/IL-1R (TIR) domain-containing adaptor protein (TIRAP) on the plasma membrane (PM) (TLR4) and endosomal subdomains (TLR7/9) to induce MyD88 oligomerization (MyDDosome) through TIR domain interactions. [11] MyD88 death domain (DD) and the intermediate domain (INT) are necessary for IL-1R-associated kinase (IRAK) binding, signaling transduction, and downstream NF-κB and IRF7 activation. [11,12] Stimulation of different TLRs triggers the association of MyD88 and induces distinct patterns of gene expression. [13,14] Recently, a study suggests that MyD88 could be rewired for glycolysis. [4] Thus, customized MyD88 signaling could not only be used for the activation of innate immunity but also to instruct the development of antigen-specific acquired immunity and metabolism. Similarly, the binding of viral RNA to RIG-I triggers RIG-I K63 polyubiquitination and mitochondrial translocation to engage and induce mitochondrial antiviral-signaling protein (MAVS) prion-like polymers (MAVSome), [15] which in turn induces TANK binding kinase 1 (TBK1)-IRF3 interaction to trigger IFN production. [16] Currently, the studies of Toll-like and RIG-I-like receptor signaling use synthetic PAMP ligands, such as poly(I:C) for TLR3 and RIG-I, LPS for TLR4, and CpG for TLR9. However, these reagents lack high signaling specificity because they can activate multiple cross-talking signaling pathways. For instance, dsRNA activates IFN pathways involving TLR3 and RIG-I/MDA5, as well as PRK (protein kinase K), to cause translational suppression; [17,18] whereas dsDNA activates TLR9, AIM2, and cGAS. [19] Potential ligand toxicity may also lead to acute cell death. [20] There remains, therefore, a criticalThe spatiotemporal organization of oligomeric protein complexes, such as the supramolecular organizing centers (SMOCs) made of MyDDosome and MAVSome, is essential for transcriptional activation of host inflammatory responses and immunometabolism. Light-inducible assembly of MyDDosome and MAVSome is presented herein to induce activation of nuclear factor-kB and type-I interferons. Enginee...

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Regulation of type I-interferon responses in the human epidermal melanocyte cell line SKMEL infected by the Ross River alphavirus

Cited by 6 publications

References 15 publications

Mayaro Virus Non-Structural Protein 2 Circumvents the Induction of Interferon in Part by Depleting Host Transcription Initiation Factor IIE Subunit 2

Mayaro Virus Non-Structural Protein 2 Circumvents the Induction of Interferon in Part by Depleting Host Transcription Initiation Factor IIE Subunit 2

In vitro comparison of three common essential oils mosquito repellents as inhibitors of the Ross River virus

Engineering Supramolecular Organizing Centers for Optogenetic Control of Innate Immune Responses

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