Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital

Evolutionary selection of pestivirus variants with altered or no microRNA dependency

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review


  1. BloodSpot: a database of healthy and malignant haematopoiesis updated with purified and single cell mRNA sequencing profiles

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Peak-valley-peak pattern of histone modifications delineates active regulatory elements and their directionality

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. BloodSpot: a database of gene expression profiles and transcriptional programs for healthy and malignant haematopoiesis

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Vis graf over relationer

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.

TidsskriftNucleic Acids Research
Udgave nummer10
Sider (fra-til)5555-5571
Antal sider17
StatusUdgivet - 4 jun. 2020

Bibliografisk note

© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.

ID: 59831517