The orf virus (ORFV) protein OV20.0 interacts with the microprocessor complex subunit DGCR8 to regulate miRNA biogenesis and ORFV infection

FEBS Lett. 2021 Dec;595(23):2897-2908. doi: 10.1002/1873-3468.14231. Epub 2021 Nov 22.

Abstract

Cellular double-stranded RNA-binding proteins (DRBPs) play important roles in the regulation of innate immune responses and microRNA (miRNA) biogenesis. The current study aimed to understand whether OV20.0, a DRBP of orf virus (ORFV), is involved in cellular RNA biogenesis via association with host DRBPs. We found that OV20.0 interacts with DiGeorge syndrome critical region 8 (DGCR8), a subunit of the miRNA processor complex, and binds to primary- and precursor-miRNA. Additionally, OV20.0 regulates DGCR8 expression in multiple ways, including through interaction with the DGCR8 protein and binding to DGCR8 mRNA. Lastly, our data show that DGCR8 plays an antiviral role against ORFV infection, whereas it is beneficial for influenza virus propagation, indicating that the underlying mechanisms could be diverse among different viruses.

Keywords: DGCR8; OV20.0; double-stranded RNA; innate immunity; orf virus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Animals
  • Dogs
  • Ecthyma, Contagious / metabolism
  • Ecthyma, Contagious / virology*
  • HEK293 Cells
  • Humans
  • Madin Darby Canine Kidney Cells
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Orf virus / pathogenicity
  • Protein Binding
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins / metabolism*
  • Viral Proteins / metabolism*

Substances

  • DGCR8 protein, human
  • MicroRNAs
  • OV20.0L protein, Orf virus
  • RNA, Messenger
  • RNA-Binding Proteins
  • Viral Proteins