A volatile from skin microbiota of flavivirus-infected host promotes mosquito attractiveness
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE195569 | GEO | 2023/01/01
REPOSITORIES: GEO
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Project description:Mosquitoes transmit many flaviviruses of global public health significance. Efficient viral transmission to mammalian hosts requires mosquito salivary factors that modulate local host responses, such as recruitment of virus-permissive myeloid cells to the bite sites. However, the specific salivary components facilitating viral transmission and their mechanisms of action remain largely unknown. Here, we showed that a female mosquito salivary gland-specific protein, named Aedes aegypti Neutrophil Recruitment Protein (AaNRP), acts as a key salivary component to facilitate the transmission of Zika (ZIKV) and dengue (DENV) viruses. AaNRP promotes a rapid influx of neutrophils followed by virus-susceptible myeloid cells toward mosquito bite sites, which facilitate establishment of local infection and systemic dissemination. Mechanistically, AaNRP engages TLR1 and TLR4 of skin resident macrophages and activates MyD88-dependent NF-κB signaling to induce the expression of neutrophil chemoattractants. Inhibition of MyD88-NF-κB with dietary resveratrol, a phytochemical, neutralizes the AaNRP effects, thus reducing flavivirus transmission by mosquitoes. This study offers mechanistic insight into saliva-aided viral transmission and provides a potential prophylactic target.
2023-05-18 | GSE232756 | GEO
Project description:A volatile from skin microbiota of flavivirus-infected host promotes mosquito attractiveness
| PRJNA801259 | ENA
Project description:Flaviviruses including dengue virus (DENV) and Zika virus (ZIKV) cause significant human disease. Co-opting cellular factors for viral protein translation and viral genome replication at the endoplasmic reticulum (ER) is a shared replication strategy, despite different clinical outcomes. While the protein products of these viruses have been studied in depth, how the RNA genomes operate inside human cells is poorly understood. Using comprehensive identification of RNA binding proteins by mass spectrometry (ChIRP-MS), we took an RNA-centric viewpoint of flaviviral infection and identified several hundred proteins associated with both DENV and ZIKV genomic RNA inside human cells. Intersection with genome-scale knockout screens assigned putative functional relevance to the RNA-protein interactions. ER RNA binding proteins such vigilin and RRBP1 directly bound viral RNA and each operated at distinct points in the life cycle of flaviviruses. Thus, this versatile strategy can elucidate features of human biology that control pathogenesis of clinically relevant viruses.
2019-04-16 | GSE109192 | GEO
Project description:Flaviviruses including dengue virus (DENV) and Zika virus (ZIKV) cause significant human disease. Co-opting cellular factors for viral protein translation and viral genome replication at the endoplasmic reticulum (ER) is a shared replication strategy, despite different clinical outcomes. While the protein products of these viruses have been studied in depth, how the RNA genomes operate inside human cells is poorly understood. Using comprehensive identification of RNA binding proteins by mass spectrometry (ChIRP-MS), we took an RNA-centric viewpoint of flaviviral infection and identified several hundred proteins associated with both DENV and ZIKV genomic RNA inside human cells. Intersection with genome-scale knockout screens assigned putative functional relevance to the RNA-protein interactions. ER RNA binding proteins such vigilin and RRBP1 directly bound viral RNA and each operated at distinct points in the life cycle of flaviviruses. Thus, this versatile strategy can elucidate features of human biology that control pathogenesis of clinically relevant viruses.
2019-04-16 | GSE109191 | GEO
Project description:Flaviviruses including dengue virus (DENV) and Zika virus (ZIKV) cause significant human disease. Co-opting cellular factors for viral protein translation and viral genome replication at the endoplasmic reticulum (ER) is a shared replication strategy, despite different clinical outcomes. While the protein products of these viruses have been studied in depth, how the RNA genomes operate inside human cells is poorly understood. Using comprehensive identification of RNA binding proteins by mass spectrometry (ChIRP-MS), we took an RNA-centric viewpoint of flaviviral infection and identified several hundred proteins associated with both DENV and ZIKV genomic RNA inside human cells. Intersection with genome-scale knockout screens assigned putative functional relevance to the RNA-protein interactions. ER RNA binding proteins such vigilin and RRBP1 directly bound viral RNA and each operated at distinct points in the life cycle of flaviviruses. Thus, this versatile strategy can elucidate features of human biology that control pathogenesis of clinically relevant viruses.
2019-04-16 | GSE109193 | GEO
Project description:Flaviviruses including dengue virus (DENV) and Zika virus (ZIKV) cause significant human disease. Co-opting cellular factors for viral protein translation and viral genome replication at the endoplasmic reticulum (ER) is a shared replication strategy, despite different clinical outcomes. While the protein products of these viruses have been studied in depth, how the RNA genomes operate inside human cells is poorly understood. Using comprehensive identification of RNA binding proteins by mass spectrometry (ChIRP-MS), we took an RNA-centric viewpoint of flaviviral infection and identified several hundred proteins associated with both DENV and ZIKV genomic RNA inside human cells. Intersection with genome-scale knockout screens assigned putative functional relevance to the RNA-protein interactions. ER RNA binding proteins such vigilin and RRBP1 directly bound viral RNA and each operated at distinct points in the life cycle of flaviviruses. Thus, this versatile strategy can elucidate features of human biology that control pathogenesis of clinically relevant viruses.
2019-04-16 | GSE109190 | GEO
Project description:Zika virus (ZIKV) infection causes microcephaly and has been linked to other brain abnormalities. How ZIKV impairs brain development and function remains elusive. Here we systematically profiled transcriptomes of human neural progenitor cells (hNPCs) and astrocytes exposed to Asian ZIKVC, African ZIKVM, and Dengue virus (DENV). DENV causes distinct gene expression changes; and ZIKV has a broader impact on the expression of gene involved in DNA replication and repair. While overall expression profiles are similar, ZIKVC, but not ZIKVM, induces upregulation of viral response genes. Upon ZIKV infection, astrocytes exhibit more prominent transcriptome changes than hNPCs, particularly enriching genes related to inflammatory response and cytokine production pathways. Our analyses reveal cell-type- and strain-specific molecular signatures associated with ZIKV infection, and identify astrocytes as a major direct target of ZIKV. Further investigation of ZIKV-host interactions based our transcriptomic datasets may help to illuminate neural virulence determinants of ZIKV in patients. Gene Expression Analyses of the cells infected with different flaviviruses
2016-08-23 | E-GEOD-80434 | biostudies-arrayexpress
Project description:Dengue virus (DENV) and Zika virus (ZIKV) are single-stranded (+)-sense RNA viruses that infect humans and mosquitoes, posing a significant health risk in tropical and subtropical regions. Mature virions are composed of an icosahedral shell of envelope (E) and membrane (M) proteins circumscribing a lipid bilayer, which in turn contains a complex of the approximately 11 kb genomic RNA with capsid (C) proteins. Whereas the structure of the envelope is clearly defined, the structure of the packaged genome in complex with C proteins remains elusive. Here, we investigate the interactions of C proteins with viral RNA, in solution and inside mature virions, via footprinting and cross-linking experiments. We demonstrate that C protein interactions with DENV and ZIKV genomes saturate at an RNA:C protein ratio below 1:250, and that binding site lengths on the genome exhibit a bimodal distribution, suggesting that RNA-C protein complexes occur in singlets or pairs. We show that interaction sites are preferentially sites with low base pairing, as measured by previously measured SHAPE reactivity indicating structuredness. We found no preference for specific sequence motifs or nucleotide composition. However, RNA-C protein binding sites are strongly associated with long-range RNA-RNA interaction sites, particularly inside virions. This helps to explain the need of C protein for viral genome packaging: the protein could coordinate those key interactions, promoting proper packing of viral RNA. Such sites are thus possible targets for drug development strategies against these and related viruses.
2022-12-31 | GSE173463 | GEO
Project description:Zika virus (ZIKV) and dengue virus (DENV) are members of the Flaviviridae family of RNA viruses and cause severe disease in humans. ZIKV and DENV share over 90% of their genome sequences, however the clinical features of Zika and dengue infections are very different reflecting tropism and cellular effects. Here, we used simultaneous RNA sequencing and ribosome footprinting to define the transcriptional and translational dynamics of ZIKV and DENV infection in human neuronal progenitor cells (hNPCs). The gene expression data showed induction of aminoacyl tRNA synthetases (ARS) and the translation-activating PIM1 kinase indicating an increase in RNA translation capacity. The data also reveal activation of different cell stress reponses, with ZIKV triggering a BACH1/2 redox program, and DENV activating the ETF/CHOP endoplasmatic reticulum (ER) stress program. The RNA translation data highlight activation of polyamine metabolism through changes in key enzymes and their regulators. This pathway is needed for eIF5A hypusination and has been implicated viral translation and replication. Concerning the viral RNA genomes, ribosome occupancy readily identifies highly translated open reading frames and a novel upstream ORF (uORF) in the DENV genome. Together, our data highlight both the cellular stress response and also the activation of RNA translation and polyamine metabolism during DENV and ZIKV infection.
2022-07-06 | GSE207347 | GEO
Project description:Zika virus (ZIKV) infection causes microcephaly and has been linked to other brain abnormalities. How ZIKV impairs brain development and function remains elusive. Here we systematically profiled transcriptomes of human neural progenitor cells (hNPCs) exposed to Asian ZIKVC, African ZIKVM, and Dengue virus (DENV). DENV causes distinct gene expression changes; and ZIKV has a broader impact on the expression of gene involved in DNA replication and repair. While overall expression profiles are similar, ZIKVC, but not ZIKVM, induces upregulation of viral response genes. Our analyses reveal virus- and strain-specific molecular signatures associated with ZIKV infection. Further investigation of ZIKV-host interactions based our transcriptomic datasets may help to illuminate neural virulence determinants of ZIKV in patients.
2016-08-23 | GSE80434 | GEO