Evolutionary selection of pestivirus variants with altered or no miRNA dependency
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA612347 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11300549.fastq.gz | Fastqsanger.gz | |||
| SRR11300550.fastq.gz | Fastqsanger.gz | |||
| SRR11300551.fastq.gz | Fastqsanger.gz | |||
| SRR11300552.fastq.gz | Fastqsanger.gz | |||
| SRR11300553.fastq.gz | Fastqsanger.gz |
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Project description:Host microRNA (miRNA) dependency is a hallmark of the human pathogen hepatitis C virus (HCV) and was recently also described for the related pestiviruses, which are important livestock pathogens. HCV critically depends on the liver-specific miR-122, whereas the broadly expressed let-7 and miR-17 families bind two sites (S1 and S2) in the pestiviral 3’ untranslated region (UTR). Here, we elucidated the miRNA dependency of bovine viral diarrhea virus (BVDV) and confirmed its critical dependence on miR-17 and Argonaute 2 (AGO2). Let-7 binding to S1 had only minor effect on virus production but was required for full translational efficiency. Evolutionary selection experiments using seed site randomized genomes revealed that tropism could be re-directed to different miRNAs. AGO cross-linking and immunoprecipitation (AGO-CLIP) and miRNA antagonism demonstrated that these alternative variants bound and depended on the corresponding miRNAs. Furthermore, we identified variants with miRNA independent replication through acquisition of compensatory mutations near the genomic 3’ terminus. Rescue experiments using miRNA mimics demonstrated that miRNA binding and 3’ mutagenesis contribute to replication through mutually exclusive mechanisms. Our findings illustrate that pestiviruses, although capable of miRNA independent replication, took advantage of miRNAs as essential host factors, suggesting a favorable path during evolutionary adaptation.
2020-03-13 | GSE146910 | GEO
Project description:Host microRNA (miRNA) dependency is a hallmark of the human pathogen hepatitis C virus (HCV) and was also described for the related pestiviruses, which are important livestock pathogens. The liver-specific miR-122 binds within the HCV 5' untranslated region (UTR), whereas the broadly expressed let-7 and miR-17 families bind two sites (S1 and S2, respectively) in the pestiviral 3' UTR. Here, we dissected the mechanism of miRNA dependency of the pestivirus bovine viral diarrhea virus (BVDV). Argonaute 2 (AGO2) and miR-17 binding were essential for viral replication, whereas let-7 binding was mainly required for full translational efficiency. Furthermore, using seed site randomized genomes and evolutionary selection experiments, we found that tropism could be redirected to different miRNAs. AGO cross-linking and immunoprecipitation (CLIP) experiments and miRNA antagonism demonstrated that these alternative variants bound and depended on the corresponding miRNAs. Interestingly, we also identified miRNA-independent variants that were obtained through acquisition of compensatory mutations near the genomic 3' terminus. Rescue experiments demonstrated that miRNA binding and 3' mutagenesis contribute to replication through mutually exclusive mechanisms. Altogether, our findings suggest that pestiviruses, although capable of miRNA-independent replication, took advantage of miRNAs as essential host factors, suggesting a favorable path during evolutionary adaptation.
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Project description:Atypical porcine pestivirus Genome sequencing
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Project description:Sexual selection involves mate preference behavior and is a critical determinant for natural selection and evolutionary biology. Previously an environmental compound (fungicide vinclozolin) was found to promote epigenetic transgenerational inheritance of modified mate selection characteristics in all progeny for three generations after exposure of a gestating female. The current study investigated gene networks involved in various regions of the brain that correlated with the mate preference behavior altered in F3-Vinclozolin lineage animals. Statistically significant correlations of differentially expressed gene clusters and modules were identified to associate with specific mate preference behaviors. This novel systems biology approach identified critical gene networks involved in mate preference behavior and demonstrated the ability of environmental factors to promote epigenetic transgenerational inheritance of this altered evolutionary biology determinant. Combined observations elucidate the potential molecular control of mate preference behavior and suggests environmental epigenetics can have a role in evolutionary biology. We used Affymetrix Rat Gene 1.0 ST microarrays to determine genes expressed differentially in F3 Vinclozolin lineage male or female rats' 6 brain areas - amygdala (Amy), hippocampus (Hipp), olfactory bulb (OlfB), cingulate cortex (CngCtx), entorhinal cortex (EnCtx), and preoptic area-anterior hypothalamus (POAH) - due to Vinclozolin treatments of their grand-grandmothers (F0).
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Project description:Sexual selection involves mate preference behavior and is a critical determinant for natural selection and evolutionary biology. Previously an environmental compound (fungicide vinclozolin) was found to promote epigenetic transgenerational inheritance of modified mate selection characteristics in all progeny for three generations after exposure of a gestating female. The current study investigated gene networks involved in various regions of the brain that correlated with the mate preference behavior altered in F3-Vinclozolin lineage animals. Statistically significant correlations of differentially expressed gene clusters and modules were identified to associate with specific mate preference behaviors. This novel systems biology approach identified critical gene networks involved in mate preference behavior and demonstrated the ability of environmental factors to promote epigenetic transgenerational inheritance of this altered evolutionary biology determinant. Combined observations elucidate the potential molecular control of mate preference behavior and suggests environmental epigenetics can have a role in evolutionary biology. We used Affymetrix Rat Gene 1.0 ST microarrays to determine genes expressed differentially in F3 Vinclozolin lineage male or female rats' 6 brain areas - amygdala (Amy), hippocampus (Hipp), olfactory bulb (OlfB), cingulate cortex (CngCtx), entorhinal cortex (EnCtx), and preoptic area-anterior hypothalamus (POAH) - due to Vinclozolin treatments of their grand-grandmothers (F0). For each of 6 brain areas of male or female rats (female: amygdala (F-Amy), cingulate cortex (F-CngCTX), enterorhinal cortex (F-EnCTX), hippocampus (F-Hipp), olfactory bulbs (F-OlfB), and preoptic area-anterior hypothalamus (F-POAH); male: amygdala (M-Amy), cingulate cortex (M-CngCTX), enterorhinal cortex (M-EnCTX), hippocampus (M-Hipp), olfactory bulbs (M-OlfB), and preoptic area-anterior hypothalamus (M-POAH)), RNA samples from 2 treatment groups - F3 Control lineage (Con) or F3 Vinclozolin lineage (Vin) - were compared to each other. Each of treatment groups contained 4-6 biological replicas for each brain region. RNA for each replica was isolated from an individual animal in order to compare to individual animal mate preference behavior studied with the same rats before sacrifice. Totally, 132 RNA samples from 24 animals (6 male F3 Control, 6 male F3 Vinclozolin,6 female F3 Control, and 6 female F3 Vinclozolin) were isolated and studied.
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