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

• Published in: FEBS letters Vol. 595; no. 23; pp. 2897 - 2908
• Main Authors: Liao, Guan‐Ru, Tseng, Yeu‐Yang, Tseng, Ching‐Yu, Lo, Chen‐Yu, Hsu, Wei‐Li
• Format: Journal Article
• Language: English
• Published: England 01.12.2021
• Subjects: A549 Cells; Animals; biogenesis; DGCR8; Dogs; double‐stranded RNA; Ecthyma, Contagious - metabolism; Ecthyma, Contagious - virology; HEK293 Cells; Humans; innate immunity; Madin Darby Canine Kidney Cells; microRNA; MicroRNAs - genetics; MicroRNAs - metabolism; Orf virus; Orf virus - pathogenicity; Orthomyxoviridae; OV20.0; Protein Binding; RNA, Messenger - metabolism; RNA-Binding Proteins - metabolism; Viral Proteins - metabolism; DGCR8; orf virus; double-stranded RNA; innate immunity; OV20.0
• ISSN: 0014-5793; 1873-3468; 1873-3468
• DOI: 10.1002/1873-3468.14231

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. We show that the orf virus (ORFV) dsRNA binding protein (DRBP) and virulence factor OV20.0 facilitates ORFV infection by modulating miRNA biogenesis via multiple mechanisms, including (1) interaction with pri‐miRNA, (2) binding and interfering with the function of DiGeorge syndrome critical region 8 (DGCR8), a subunit of the miRNA processor complex, (3) sequestering pre‐miRNA, and (4) affecting miRNA maturation, possibly by interacting with the DRBP PACT in the cytoplasm.