Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA387718 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:RNA interference (RNAi) functions as a potent antiviral immunity in plants and invertebrates, however whether RNAi plays antiviral roles in mammals remains unclear. Here, using human enterovirus 71 (HEV71) as a model, we showed HEV71 3A protein as an authentic viral suppressor of RNAi during viral infection. When the 3A-mediated RNAi suppression was impaired, the mutant HEV71 readily triggered the production of abundant HEV71-derived small RNAs with canonical siRNA properties in cells and mice. These virus-derived siRNAs were produced from viral dsRNA replicative intermediates in a Dicer-dependent manner, loaded into AGO, and were fully active in degrading cognate viral RNAs. Recombinant HEV71 deficient in 3A-mediated RNAi suppression was significantly restricted in human somatic cells and mice, whereas Dicer-deficiency rescued HEV71 infection independently of type I interferon response. Thus, RNAi can function as an antiviral immunity, which is induced and suppressed by a human virus, in mammals.
2017-08-01 | GSE99252 | GEO
Project description:Plants and invertebrates protect themselves from viruses through RNA interference (RNAi), yet it remains unknown whether this defense mechanism exists in mammals. Antiviral RNAi involves the processing of viral long double-stranded (ds) RNA molecules into small interfering RNAs (siRNAs) by the ribonuclease (RNAse) III Dicer. These siRNAs are incorporated into effector complex(es) containing members of the Argonaute (Ago) protein family and guide silencing of complementary target viral RNAs. Here, we detect the accumulation of phased Dicer-dependent virus-derived siRNA (viRNAs) and demonstrate their loading into Ago2 after infection of mouse embryonic stem (ES) cells with Encephalomyocarditis virus (EMCV). We further show that the production of these viRNAs is drastically reduced, yet not completely abolished, if ES cells are first induced to differentiate before infection. Finally, we reveal that the mammalian virus Nodamura virus (NoV) encodes for a protein that counteracts such antiviral RNAi in ES cells supporting the existence of an effective RNAi-based immunity in mammals. Infection of wild-type or mutant mouse ES cells and analysis of small RNAs from total extracts or immunoprecipitated components of the RNAi pathway
2013-10-10 | E-GEOD-43153 | biostudies-arrayexpress
Project description:Plants and invertebrates protect themselves from viruses through RNA interference (RNAi), yet it remains unknown whether this defense mechanism exists in mammals. Antiviral RNAi involves the processing of viral long double-stranded (ds) RNA molecules into small interfering RNAs (siRNAs) by the ribonuclease (RNAse) III Dicer. These siRNAs are incorporated into effector complex(es) containing members of the Argonaute (Ago) protein family and guide silencing of complementary target viral RNAs. Here, we detect the accumulation of phased Dicer-dependent virus-derived siRNA (viRNAs) and demonstrate their loading into Ago2 after infection of mouse embryonic stem (ES) cells with Encephalomyocarditis virus (EMCV). We further show that the production of these viRNAs is drastically reduced, yet not completely abolished, if ES cells are first induced to differentiate before infection. Finally, we reveal that the mammalian virus Nodamura virus (NoV) encodes for a protein that counteracts such antiviral RNAi in ES cells supporting the existence of an effective RNAi-based immunity in mammals.
2013-10-10 | GSE43153 | GEO
Project description:While the intrinsic antiviral cell defenses of many kingdoms utilize pathogen-specific small RNAs, the antiviral response of chordates is primarily protein-based and not uniquely tailored to the incoming microbe. In an effort to explain this evolutionary bifurcation, we determined whether antiviral RNA interference (RNAi) was sufficient to replace the protein-based type I interferon (IFN-I) system of mammals. To this end, we recreated an RNAi-like response in mammals and determined its effectiveness to combat influenza A virus in vivo in the presence and absence of the canonical IFN-I system. Mammalian antiviral RNAi, elicited by either host- or virus-derived small RNAs, effectively attenuated virus and prevented disease independently of the innate immune response. These data find that chordates could have utilized RNAi as their primary antiviral cell defense and suggest that the IFN-I system emerged as a result of natural selection imposed by ancient pathogens.
2015-10-03 | GSE73698 | GEO
Project description:Bats harbor highly virulent viruses that can infect other mammals, including humans, posing questions about their immune tolerance mechanisms. Bat cells employ multiple strategies to limit virus replication and virus-induced immunopathology, but the coexistence of bats and fatal viruses remains poorly understood. Here, we investigated the antiviral RNA interference (RNAi) pathway in bat cells and discovered that they have an enhanced antiviral RNAi response, producing canonical viral small interfering RNAs (vsiRNAs) upon Sindbis virus (SINV) infection that were missing in human cells. Disruption of Dicer function resulted in increased viral load for three different RNA viruses in bat cells, indicating an interferon-independent antiviral pathway. Furthermore, our findings reveal the simultaneous engagement of Dicer and pattern-recognition receptors (PRRs), such as retinoic acid-inducible gene I (RIG-I), with double-stranded RNA, suggesting that Dicer attenuates the interferon response initiation in bat cells. These insights advance our comprehension of the distinctive strategies bats employ to coexist with viruses.
2024-07-12 | PXD053906 | Pride
Project description:We report the cloning and sequencing of both endogenous small RNAs and virus-derived siRNAs produced by the antiviral RNAi pathway in Drosophila. We find that a diverse panel of viruses are targeted by the RNAi pathway in Drosophila to produce abundant virus-derived siRNAs, and these siRNAs map to various locations within the viral genomes. Knockdown of various RNAi and miRNA pathway components alters the levels of these viral small RNAs. Drosophila DL1 cells were treated with dsRNA for 3 days to deplete factors involved in the antiviral RNAi pathway and miRNA pathway, then were challenged with one of four viruses for 4 days. Total RNA was collected, and the small RNA populations from 15-29 nt were cloned and sequenced.
2013-01-01 | E-GEOD-43031 | biostudies-arrayexpress
Project description:Small RNAs were profiled during Sendai virus infection of human A549 cells to identify changes in microRNA abundance during the cellular antiviral response. Examination of microRNA abundance during Sendai virus infection.
2013-06-10 | E-GEOD-43966 | biostudies-arrayexpress
Project description:Small RNAs play a critical role in host-pathogen interaction. In insects, for instance, small RNA-mediated silencing or RNA interference (RNAi) represents the main antiviral defense system. However, the antiviral role of RNAi has not been clearly proven in higher vertebrates. On the contrary, it is well established that the cell response relies on the recognition of viral RNAs by host pattern recognition receptors (PRR) to trigger the activation of the interferon pathway. Based on this evidence, we wished to contribute to this research field by identifying and characterizing small non-coding RNAs produced in mammalian cells upon RNA virus infection. We focused on Sindbis virus (SINV), the prototypical arbovirus, which by definition, is able to infect both vertebrate hosts and invertebrate vectors and triggers the interferon pathway or RNAi, respectively. Taking advantage of large scale sequencing, we cloned and sequenced small RNAs from both mock and SINV-infected mammalian cells (HEK 293 and VERO). We identified a novel population of viral small RNAs (vsRNAs) that accumulate as 20 to 30 nt species during infection. We assessed that this viral small RNA population is modified in 3'end and derived from the activation of the cellular antiviral endoribonuclease RNaseL. Altogether our results indicate a potential role for the SINV-derived small RNAs in the host defense mechanism.
2013-11-19 | E-GEOD-48831 | biostudies-arrayexpress
Project description:Small RNAs were profiled during influenza A virus infection of human A549 cells to identify changes in microRNA abundance during the cellular antiviral response. Examination of microRNA abundance during influenza A virus infection.
2013-09-15 | E-GEOD-48036 | biostudies-arrayexpress
Project description:We report the cloning and sequencing of both endogenous small RNAs and virus-derived siRNAs produced by the antiviral RNAi pathway in Drosophila. We find that a diverse panel of viruses are targeted by the RNAi pathway in Drosophila to produce abundant virus-derived siRNAs, and these siRNAs map to various locations within the viral genomes. Knockdown of various RNAi and miRNA pathway components alters the levels of these viral small RNAs.
2013-01-01 | GSE43031 | GEO