Identification of a novel antiviral micro-RNA targeting the NS1 protein of the H1N1 pandemic human influenza virus and a corresponding viral escape mutation

Bavagnoli, Laura; Campanini, Giulia; Forte, Maurizio; Ceccotti, Giorgia; Percivalle, Elena; Bione, Silvia; Lisa, Antonella; Baldanti, Fausto; Maga, Giovanni

doi:10.1016/j.antiviral.2019.104593

Cited by 18 publications

(23 citation statements)

References 35 publications

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“…Sequence matches to the human miRNAs hsa-miR-1307–3p and hsa-miR-1304–3p were located within the broader conserved RNA motif S2m. Interestingly, a recent study of IAV H1N1 provided supporting functional evidence of hsa-miR-1307–3p in mediating antiviral responses and inhibiting viral replication ( 32 ). We discuss a possible similar role of human miR-1307 in SARS-CoV-2 infection below (see Discussion ).…”

Section: Resultsmentioning

confidence: 97%

“…mir-1307 expression has been shown to be dysregulated in newborns with chronic lung disease ( 46 ). Importantly, the study by Bavagnoli et al demonstrated a functional role of miR-1307 in the regulation of viral replication in the influenza A virus H1N1, which was the pathogen responsible for the 2009 H1N1 pandemic ( 32 ). Their study predicted sequence complementarity of miR-1307 to the H1N1 nonstructural protein 1 (NS1), which functions to limit interferon and proinflammatory responses thus allowing the virus to evade host innate and adaptive immunity and replicate efficiently in infected cells.…”

Section: Discussionmentioning

confidence: 99%

Section: Analysis Of Sars-cov-2 Variant Combinationsmentioning

confidence: 99%

“…(C) Putative base-pairings between human miRNA hsa-miR-1307–3p and the SARS-CoV-2 3’-UTR. The base-pairings of miR-1307–3p against the H1N1 NS1 C112A mutant and the H1N1 NS1 wild type sequences were based on ( 32 ) and updated using bifold prediction ( 53 ).…”

Section: Figmentioning

confidence: 99%

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Conserved Genomic Terminals of SARS-CoV-2 as Co-evolving Functional Elements and Potential Therapeutic Targets

Chan

Choi

Schork

2020

Preprint

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ABSTRACTTo identify features in the genome of the SARS-CoV-2 pathogen responsible for the COVID-19 pandemic that may contribute to its viral replication, host pathogenicity, and vulnerabilities, we investigated how and to what extent the SARS-CoV-2 genome sequence differs from other well-characterized human and animal coronavirus genomes. Our analyses suggest the presence of unique sequence signatures in the 3’-untranslated region (UTR) of betacoronavirus lineage B, which phylogenetically encompasses SARS-CoV-2, SARS-CoV, as well as multiple groups of bat and animal coronaviruses. In addition, we identified genome-wide patterns of variation across different SARS-CoV-2 strains that likely reflect the effects of selection. Finally, we provide evidence for a possible host microRNA-mediated interaction between the 3’-UTR and human microRNA hsa-miR-1307-3p based on predicted, yet extensive, complementary base-pairings and similar interactions involving the Influenza A H1N1 virus. This interaction also suggests a possible survival mechanism, whereby a mutation in the SARS-CoV-2 3’-UTR leads to a weakened host immune response. The potential roles of host microRNAs in SARS-CoV-2 replication and infection, and the exploitation of conserved features in the 3’-UTR as therapeutic targets warrant further investigation.

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Section: Resultsmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Analysis Of Sars-cov-2 Variant Combinationsmentioning

confidence: 99%

Section: Figmentioning

confidence: 99%

See 2 more Smart Citations

Conserved Genomic Terminals of SARS-CoV-2 as Co-evolving Functional Elements and Potential Therapeutic Targets

Chan

Choi

Schork

2020

Preprint

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“…miR-1307 expression has been shown to be dysregulated in newborns with chronic lung disease (56). Importantly, the study by Bavagnoli et al demonstrated a functional role of miR-1307 in the regulation of viral replication in the influenza A virus H1N1, which was the pathogen responsible for the 2009 H1N1 pandemic (40). Their study predicted sequence complementarity of miR-1307 to H1N1 nonstructural protein 1 (NS1), which functions to limit interferon and proinflammatory responses, thus allowing the virus to evade host innate and adaptive immunity and replicate efficiently in infected cells.…”

Section: Discussionmentioning

confidence: 99%

Conserved Genomic Terminals of SARS-CoV-2 as Coevolving Functional Elements and Potential Therapeutic Targets

Chan

Choi

Schork

2020

mSphere

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected over 40 million people worldwide, with over 1 million deaths as of October 2020 and with multiple efforts in the development and testing of antiviral drugs and vaccines under way. In order to gain insights into SARS-CoV-2 evolution and drug targets, we investigated how and to what extent the SARS-CoV-2 genome sequence differs from those of other well-characterized human and animal coronavirus genomes, as well as how polymorphic SARS-CoV-2 genomes are generally. We ultimately sought to identify features in the SARS-CoV-2 genome that may contribute to its viral replication, host pathogenicity, and vulnerabilities. Our analyses suggest the presence of unique sequence signatures in the 3′ untranslated region (3′-UTR) of betacoronavirus lineage B, which phylogenetically encompasses SARS-CoV-2 and SARS-CoV as well as multiple groups of bat and animal coronaviruses. In addition, we identified genome-wide patterns of variation across different SARS-CoV-2 strains that likely reflect the effects of selection. Finally, we provide evidence for a possible host-microRNA-mediated interaction between the 3′-UTR and human microRNA hsa-miR-1307-3p based on the results of multiple computational target prediction analyses and an assessment of similar interactions involving the influenza A H1N1 virus. This interaction also suggests a possible survival mechanism, whereby a mutation in the SARS-CoV-2 3′-UTR leads to a weakened host immune response. The potential roles of host microRNAs in SARS-CoV-2 replication and infection and the exploitation of conserved features in the 3′-UTR as therapeutic targets warrant further investigation. IMPORTANCE The coronavirus disease 2019 (COVID-19) outbreak is having a dramatic global effect on public health and the economy. As of October 2020, SARS-CoV-2 has been detected in over 189 countries, has infected over 40 million people, and is responsible for more than 1 million deaths. The genome of SARS-CoV-2 is small but complex, and its functions and interactions with human host factors are being studied extensively. The significance of our study is that, using extensive SARS-CoV-2 genome analysis techniques, we identified potential interacting human host microRNA targets that share similarity with those of influenza A virus H1N1. Our study results will allow the development of virus-host interaction models that will enhance our understanding of SARS-CoV-2 pathogenesis and motivate the exploitation of both the interacting viral and host factors as therapeutic targets.

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HCV eradication with DAAs differently affects HIV males and females: A whole miRNA sequencing characterization

Valle-Millares

Brochado-Kith

Gómez-Sanz

et al. 2022

Biomedicine & Pharmacotherapy

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Identification of a novel antiviral micro-RNA targeting the NS1 protein of the H1N1 pandemic human influenza virus and a corresponding viral escape mutation

Cited by 18 publications

References 35 publications

Conserved Genomic Terminals of SARS-CoV-2 as Co-evolving Functional Elements and Potential Therapeutic Targets

Conserved Genomic Terminals of SARS-CoV-2 as Co-evolving Functional Elements and Potential Therapeutic Targets

Conserved Genomic Terminals of SARS-CoV-2 as Coevolving Functional Elements and Potential Therapeutic Targets

HCV eradication with DAAs differently affects HIV males and females: A whole miRNA sequencing characterization

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