JNK pathway restricts DENV2, ZIKV and CHIKV infection by activating complement and apoptosis in mosquito salivary glands

Chowdhury, Avisha; Modahl, Cassandra M.; Tan, Siok Thing; Xiang, Benjamin Wong Wei; Missé, Dorothée; Vial, Thomas; Kini, R. Manjunatha; Pompon, Julien

doi:10.1371/journal.ppat.1008754

Cited by 52 publications

(104 citation statements)

References 84 publications

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“…In addition, the findings from a study about JNK by Avisha Chowdhury suggest that the pathways have a broad antiviral function against DENV, depending on apoptosis induction and the complement system. Moreover, activated c-JUN participates in controlling the rearrangement of membrane structures, which is induced by DENV and required for replication ( 49 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of COVID-19 and Dengue Host Factor Interaction Networks Based on Integrative Bioinformatics Analyses

Zheng

Liu

et al. 2021

Front. Immunol.

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BackgroundThe outbreak of Coronavirus disease 2019 (COVID-19) has become an international public health crisis, and the number of cases with dengue co-infection has raised concerns. Unfortunately, treatment options are currently limited or even unavailable. Thus, the aim of our study was to explore the underlying mechanisms and identify potential therapeutic targets for co-infection.MethodsTo further understand the mechanisms underlying co-infection, we used a series of bioinformatics analyses to build host factor interaction networks and elucidate biological process and molecular function categories, pathway activity, tissue-specific enrichment, and potential therapeutic agents.ResultsWe explored the pathologic mechanisms of COVID-19 and dengue co-infection, including predisposing genes, significant pathways, biological functions, and possible drugs for intervention. In total, 460 shared host factors were collected; among them, CCL4 and AhR targets were important. To further analyze biological functions, we created a protein-protein interaction (PPI) network and performed Molecular Complex Detection (MCODE) analysis. In addition, common signaling pathways were acquired, and the toll-like receptor and NOD-like receptor signaling pathways exerted a significant effect on the interaction. Upregulated genes were identified based on the activity score of dysregulated genes, such as IL-1, Hippo, and TNF-α. We also conducted tissue-specific enrichment analysis and found ICAM-1 and CCL2 to be highly expressed in the lung. Finally, candidate drugs were screened, including resveratrol, genistein, and dexamethasone.ConclusionsThis study probes host factor interaction networks for COVID-19 and dengue and provides potential drugs for clinical practice. Although the findings need to be verified, they contribute to the treatment of co-infection and the management of respiratory disease.

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Section: Discussionmentioning

confidence: 99%

Identification of COVID-19 and Dengue Host Factor Interaction Networks Based on Integrative Bioinformatics Analyses

Zheng

Liu

et al. 2021

Front. Immunol.

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“…The expression of AMPs is regulated by the AaSR-C/AaMCR complex for potent anti-DENV activity. Additionally, previous studies have also suggested that AMPs play crucial roles in mosquito immune defense against DENV ( 31 – 33 ). Therefore, we hypothesized that TEP1 controls DENV replication by regulating the expression of AMPs.…”

Section: Resultsmentioning

confidence: 96%

“…Pathogenic cell surface proteins are recognized by immune receptors and trigger downstream transcription factors such as Rel1 (Toll pathway), Rel2 (Imd pathway), and STAT (JAK-STAT pathway). Previous studies have evaluated how the expression of AMPs are induced by DENV infection in mosquitoes, and they exhibit antiviral activities ( 6 , 8 , 18 , 20 ). We further demonstrated that transgenic mosquitoes with TEP1 loss-of-function inhibited the expression of two AMPs and the transcription factor Rel2 of the Imd pathway.…”

Section: Discussionmentioning

confidence: 99%

“…The mechanisms involved in the regulation of AMPs via immune pathways have mainly been studied in Drosophila ( 6 , 8 , 19 ). In mosquitoes, Toll, Imd, and JAK-STAT pathways are activated during pathogen infection ( 6 , 8 , 19 , 20 ). Pathogenic surface proteins are recognized by immune receptors and trigger downstream transcription factors, such as Rel1 (Toll pathway), Rel2 (Imd pathway), and STAT (JAK-STAT pathway) ( 21 ).…”

Section: Introductionmentioning

confidence: 99%

“…Then, the activated transcription factors bind to specific regulatory elements for AMP gene transcription initiation ( 6 , 8 , 19 ). The JAK-STAT pathway has been shown to be activated by viral infection in mosquitoes ( 6 , 8 , 20 ). Previous studies also report that AMP expression may be induced by DENV infection in mosquitoes, and AMPs exhibit antiviral activity ( 6 , 8 , 18 , 20 ).…”

Section: Introductionmentioning

confidence: 99%

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A Thioester-Containing Protein Controls Dengue Virus Infection in Aedes aegypti Through Modulating Immune Response

Weng

et al. 2021

Front. Immunol.

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Complement-like proteins in arthropods defend against invading pathogens in the early phases of infection. Thioester-containing proteins (TEPs), which exhibit high similarity to mammalian complement C3, are thought to play a key role in the innate immunity of arthropods. We identified and characterized anti-dengue virus (DENV) host factors, in particular complement-like proteins, in the mosquito Aedes aegypti. Our results indicate that TEP1 limits DENV infection in Ae. aegypti. We showed that TEP1 transcription is highly induced in mosquitoes following DENV infection. Silencing TEP1 resulted in the up-regulation of viral RNA and proteins. In addition, the production of infectious virus particles increased in the absence of TEP1. We generated a transgenic mosquito line with a TEP1 loss-of-function phenotype under a blood meal-inducible promoter. We showed that viral protein and titers increased in transgenic mosquitoes after an infectious blood meal. Interestingly, expression of transcription factor Rel2 and certain anti-microbial peptides (AMPs) were inhibited in transgenic mosquitoes. Overall, our results suggest that TEP1 regulates the immune response and consequently controls the replication of dengue virus in mosquitoes. This finding provides new insight into the molecular mechanisms of mosquito host factors in the regulation of DENV replication.

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The gut microbiome of Helicoverpa armigera enhances immune response to baculovirus infection via suppression of Duox‐mediated reactive oxygen species

Tian

Guo

Michaud

et al. 2023

Pest Management Science

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BACKGROUNDBaculoviruses such as Helicoverpa armigera nucleopolyhedrovirus (HearNPV) infect their lepidopteran hosts via the larval midgut where they interact with host immune responses and gut microbiota. Here we demonstrate that gut microbiota proliferating in response to HearNPV infection promote larval immune responses which impede the infection process.RESULTSThe microbial load of the larval midgut increased following HearNPV infection, due primarily to increases in Enterococcus spp., whereas most other bacterial genera declined, with Firmicutes replacing Proteobacteria as the dominant phylum. Injection of abdominal prolegs of infected larvae with H2O2 promoted viral infection, diminished microbial abundance, and accelerated larval death, mimicking the effects of HearNPV infection, which up‐regulated dual oxidase (Duox) expression, increasing H2O2 levels in the midgut. Knockdown of Duox with RNAi reduced H2O2 production in the guts of infected larvae, increased bacterial loads, decreased viral replication, and improved larval survival. Germ‐free larvae were more susceptible to HearNPV than control larvae, exhibiting greater expression of Duox, higher levels of H2O2, and lower survival. Replenishment of gut bacteria in germ‐free larvae restored the base‐line immunity to HearNPV observed in normal larvae. Enterococcus spp., Levilactobacillus brevis, and Lactobacillus sp. bacteria were isolated and implicated in immunity restoration via replenishment in germ‐free larvae.CONCLUSIONThese findings illuminate how gut microbiota play important roles in larval defense against oral baculovirus infection, and suggest novel avenues of investigation to enhance the efficacy of baculoviruses and improve control of lepidopteran pests. © 2023 Society of Chemical Industry.

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JNK pathway restricts DENV2, ZIKV and CHIKV infection by activating complement and apoptosis in mosquito salivary glands

Cited by 52 publications

References 84 publications

Identification of COVID-19 and Dengue Host Factor Interaction Networks Based on Integrative Bioinformatics Analyses

Identification of COVID-19 and Dengue Host Factor Interaction Networks Based on Integrative Bioinformatics Analyses

A Thioester-Containing Protein Controls Dengue Virus Infection in Aedes aegypti Through Modulating Immune Response

The gut microbiome of Helicoverpa armigera enhances immune response to baculovirus infection via suppression of Duox‐mediated reactive oxygen species

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