ABSTRACT
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has had a tremendous impact worldwide. Mapping virus-host interactions is critical to understand disease progression. MicroRNAs (miRNAs) are important RNA regulators, but their interaction with SARS-CoV-2 RNA was not experimentally investigated. Here, using Argonaute (AGO) cross-linking immunoprecipitation combined with RNA proximity ligation (CLEAR-CLIP), we provide unbiased mapping of SARS-CoV-2/miRNA interactions. We identified six main regions on the viral RNA bound primarily by one specific miRNA. Targeted mutagenesis and AGO1-3 knock-down demonstrated that these interactions are not critical for virus production. Moreover, we identified perturbed regulation of cellular miRNA interactions during infection, including non-compensated viral sequestration of miR-15a-5p. Transcriptome analysis further showed that messenger (m)RNAs targeted by this miRNA are derepressed. This work delineates the interphase between miRNA regulation and SARS-CoV-2 infection and further contributes to decipher the full molecular interactome of this virus. Graphical MiRNAs are important post-transcriptional regulators hijacked by viruses. Here, Fossat et al. map the miRNA binding landscape for SARS-CoV-2 RNA. Mutagenesis of the main binding sites and Argonaute silencing show that miRNAs are not critical for replication. However, the cellular miRNA interactome is perturbed, specifically with derepression of miR-15a-5p targets.
ABSTRACT
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has had a tremendous impact worldwide. Mapping virus-host interactions is critical to understand disease progression. MicroRNAs (miRNAs) are important RNA regulators, but their interaction with SARS-CoV-2 RNA was not experimentally investigated. Here, using Argonaute (AGO) cross-linking immunoprecipitation combined with RNA proximity ligation (CLEAR-CLIP), we provide unbiased mapping of SARS-CoV-2/miRNA interactions. We identified six main regions on the viral RNA bound primarily by one specific miRNA. Targeted mutagenesis and AGO1-3 knockdown demonstrated that these interactions are not critical for virus production. Moreover, we identified perturbed regulation of cellular miRNA interactions during infection, including non-compensated viral sequestration of the miR-15 family. Transcriptome analysis further showed that mRNAs targeted by this miRNA family are derepressed. This work delineates the interphase between miRNA regulation and SARS-CoV-2 infection and further contributes to deciphering the full molecular interactome of this virus.
ABSTRACT
We estimate the willingness to take the booster dose in a representative sample of Danes. We estimate an overall willingness in the adult Danish population of about 87 percent and a willingness of about 95.5 percent among primary vaccine takers. Moreover, we show that these percentages are significantly lower among younger populations, as well as among groups who do not see COVID-19 as a threat to society, those who do not feel that they have the ability to follow recommendations ('self-efficacy'), those who do not perceive the advice of the health authorities as effective against disease spread ('response efficacy'), and those who feel that the costs of following recommendations are high ('response cost').