RNA-Seq of U2OS cells with and without IFNα2 pretreatment
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE159280 | GEO | 2020/11/18
REPOSITORIES: GEO
Similar Datasets
Project description:Heldt2012 - Influenza Virus Replication
The model describes the life cycle of influenza A virus in a mammalian cell including the following steps: attachment of parental virions to the cell membrane, receptor-mediated endocytosis, fusion of the virus envelope with the endosomal membrane, nuclear import of vRNPs, viral transcription and replication, translation of the structural viral proteins, nuclear export of progeny vRNPs and budding of new virions. It also explicitly accounts for the stabilization of cRNA by viral polymerases and NP and the inhibition of vRNP activity by M1 protein binding. In short, the model focuses on the molecular mechanism that controls viral transcription and replication.
This model is described in the article:
Modeling the intracellular dynamics of influenza virus replication to understand the control of viral RNA synthesis.
Heldt FS, Frensing T, Reichl U.
J Virol.
Abstract:
Influenza viruses transcribe and replicate their negative-sense RNA genome inside the nucleus of host cells via three viral RNA species. In the course of an infection, these RNAs show distinct dynamics, suggesting that differential regulation takes place. To investigate this regulation in a systematic way, we developed a mathematical model of influenza virus infection at the level of a single mammalian cell. It accounts for key steps of the viral life cycle, from virus entry to progeny virion release, while focusing in particular on the molecular mechanisms that control viral transcription and replication. We therefore explicitly consider the nuclear export of viral genome copies (vRNPs) and a recent hypothesis proposing that replicative intermediates (cRNA) are stabilized by the viral polymerase complex and the nucleoprotein (NP). Together, both mechanisms allow the model to capture a variety of published data sets at an unprecedented level of detail. Our findings provide theoretical support for an early regulation of replication by cRNA stabilization. However, they also suggest that the matrix protein 1 (M1) controls viral RNA levels in the late phase of infection as part of its role during the nuclear export of viral genome copies. Moreover, simulations show an accumulation of viral proteins and RNA toward the end of infection, indicating that transport processes or budding limits virion release. Thus, our mathematical model provides an ideal platform for a systematic and quantitative evaluation of influenza virus replication and its complex regulation.
With the current parameter set, the model reproduces an infection at a multiplicity of infection (MOI) of 10. Figure 2A of the paper is reproduced here, with parameters kDegRnp and kSynP changed to zeros.
Initial conditions and parameter changes that were used to obtain specific figures in the article can be found in Table A2.
The model has the correct value for kAttLo as 4.55e-04. The value of this parameter mentioned as 4.55e-02 in Table 1 of the paper is incorrect. This is checked with the author.
This model is hosted on BioModels Database
and identified
by: MODEL1307270000
.
To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource
for published quantitative kinetic models
.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to the public
domain worldwide. Please refer to CC0 Public Domain
Dedication
for more information.
2024-09-02 | BIOMD0000000463 | BioModels
Project description:Encoded model contains complete kinetics of infection for coxsackievirus B3 (CVB3), a compact and fast-acting RNA virus. The model consists of separable, detailed modules describing viral binding-delivery, translation-replication, and encapsidation. Specific module activities are dampened by the type I interferon response to viral double-stranded RNAs (dsRNAs), which is itself disrupted by viral proteinases
2021-10-26 | MODEL2110250001 | BioModels
Project description:Lipid metabolism is an intricate yet crucial cellular process co-opted by multiple viruses for replication and biogenesis. Transmembrane Protein 41B (TMEM41B) and Vacuole Membrane Protein 1 (VMP1) are two recently identified ER-resident lipid scramblases that play a role in autophagosome formation and cellular lipid metabolism. Importantly, TMEM41B is also a newly validated host dependency factor required for productive infection of several medically important enveloped RNA viruses, such as flaviviruses and human coronaviruses. However, the exact underlying mechanism of TMEM414B in modulating viral infections remains an open question. Here, we uncovered that TMEM41B and VMP1 deficiencies severely impaired replication of flavivirus and human coronavirus via multiple parallel cellular mechanisms. In accordance with previous reports, we validated that both TMEM41B and VMP1 are indispensable for all four serotypes of dengue virus (DENV) and human coronavirus OC43 (HCoV-OC43) to infect human cells, but not chikungunya virus, an alphavirus. Impaired dengue virus replication in TMEM41B and VMP1 deficient cells could induce a robust activation of innate immune RNA sensing as evidenced by hyperactivation of RIG-I and MDA5. However, this phenomenon was a consequence but not the root cause of the diminished viral replication. Notably, the impact of TMEM41B deficiency on DENV replication could be reversed by complementing the cells using exogenous unsaturated fatty acids, indicating a metabolic role for TMEM41B in flavivirus infection. Furthermore, we found that derailed cellular energy metabolism could be a contributing factor to block DENV infection as TMEM41B and VMP1 deficient cells harbored higher levels of compromised mitochondria that exhibited aberrant functions in facilitating beta-oxidation. Using lipidome and metabolome profiling of TMEM41B and VMP1 deficient cells, we further revealed that each of these genetic deficiencies result in distinctive cellular metabolic dysregulations, underlining their necessity for a balanced metabolic landscape, and strengthening the metabolic role of these ER membrane proteins in facilitating virus infection. Our results highlighted that TMEM41B and VMP1 are required for homeostasis of cellular metabolism, and this metabolic role contributes to their essentiality in facilitating DENV infection.
2022-05-11 | ST002164 | MetabolomicsWorkbench
Project description:Viruses are obligate intracellular parasites, which depend on the host cellular machineries to replicate their genome and complete their infectious cycle. Long double stranded (ds)RNA is a common viral by-product originating during RNA virus replication, which is universally sensed as a danger signal to trigger the antiviral response. As a result, viruses hide dsRNA intermediates into viral replication factories and have evolved strategies to hijack cellular proteins for their benefit. The characterization of the host factors associated to viral dsRNA and involved in viral replication remains a major challenge to develop new antiviral drugs against RNA viruses. Here, we performed anti-dsRNA immunoprecipitation followed by Mass Spectrometry to fully characterize the dsRNA interactome in Sindbis virus (SINV) infected human HCT116 cells. Among the validated factors, we characterized SFPQ (Splicing factor, proline-glutamine rich) as a new dsRNA-associated factor upon SINV infection. We proved that SFPQ is able to directly bind dsRNAs in vitro, that SFPQ association to dsRNA is independent on single-stranded (ss)RNA flanking regions in vivo and that it is able to bind the viral genome upon infection. Furthermore, we showed that either knock-down or knock-out of SFPQ reduced SINV infection in human HCT116 and SKNBE cells, suggesting that SFPQ could enhance viral replication. Overall, this study not only represents a resource to further study SINV dsRNA-associated factors upon infection but also identifies SFPQ as a new proviral dsRNA binding protein.
2024-05-22 | PXD024554 | Pride
Project description:Type I interferon-stimulated genes (ISGs) have critical roles in inhibiting virus replication and dissemination. Despite advances in understanding the molecular basis of ISG restriction, the antiviral mechanisms of many remain unclear. The 20 kDa ISG, ISG20, is a nuclear 3'-5'exonuclease with preference for single stranded RNA (ssRNA) and has been implicated in the IFN-mediated restriction of several RNA viruses. Although the exonuclease activity of ISG20 has been shown to degrade viral RNA in vitro, evidence has yet to be presented that virus inhibition in cells requires this activity. Here, we utilized a combination of an inducible, ectopic expression system and newly generated Isg20−/− mice to investigate mechanisms and consequences of ISG20-mediated restriction. Ectopically expressed ISG20 localized primarily to Cajal bodies in the nucleus and restricted replication of chikungunya and Venezuelan equine encephalitis viruses. Although restriction by ISG20 was associated with inhibition of translation of infecting genomic RNA, degradation of viral RNAs was not observed. Instead, translation inhibition of viral RNA was associated with ISG20-induced upregulation of over 100 other genes, many of which encode known antiviral effectors. ISG20 modulated the production of IFIT1, an ISG that suppresses translation of alphavirus RNAs. Consistent with this observation, the pathogenicity of IFIT1-sensitive alphaviruses was increased in Isg20−/− mice compared to wild-type viruses, but not in ISG20 ectopic-expressing cells. Our findings establish an indirect role for ISG20 in the early restriction of RNA virus replication by regulating expressionof other ISGs that inhibit translation and possibly other activities in the replication cycle.
2018-07-01 | GSE115729 | GEO
Project description:As obligate intracellular parasites, viruses rely heavily on their host cells for their replication, and therefore dysregulate several cellular processes for their benefit. In return, host cells activate multiple signaling pathways to limit viral replication and eradicate viruses. The present study explores the complex interplay between viruses and their host cells through next generation RNA sequencing. The coding transcriptome of human brain-derived U87 cells infected with Kunjin virus, Zika virus, or Yellow Fever virus were compared to the transcriptome of mock-infected cells. Changes in the abundance of several hundred mRNAs were found in each infection. Moreover, the alternative splicing of hundreds of mRNAs was found to be modulated upon viral infection.
2023-06-28 | GSE232504 | 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: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