Molecular characterization and antiviral effects of canine interferon regulatory factor 1 (CaIRF1)

BMC Vet Res. 2022 Dec 16;18(1):440. doi: 10.1186/s12917-022-03539-3.

Abstract

Background: Interferon regulatory factor 1 (IRF1) is an important transcription factor that activates the type I interferon (IFN-I) response and plays a vital role in the antiviral immune response. Although IRF1 has been identified in several mammals, little information related to its function in canines has been described.

Results: In this study, canine IRF1 (CaIRF1) was cloned. After a series of bioinformatics analyses, we found that the CaIRF1 protein structure was similar to that of other animal IRF1 proteins, including a conserved DNA-binding domain (DBD), an IRF-association domain 2 (IAD2) domain and two nuclear localization signals (NLSs). An indirect immunofluorescence assay (IFA) revealed that CaIRF1 was mainly distributed in the nucleus. Overexpression of CaIRF1 in Madin-Darby canine kidney cells (MDCK) induced high levels of interferon β (IFNβ) and IFN-stimulated response element (ISRE) promoter activation and induced interferon-stimulated gene (ISG) expression. Subsequently, we assayed the antiviral activity of CaIRF1 against vesicular stomatitis virus (VSV) and canine parvovirus type-2 (CPV-2) in MDCK cells. Overexpression of CaIRF1 effectively inhibited the viral yields of VSV and CPV-2, while knocking down of CaIRF1 expression mildly increased viral gene copies.

Conclusions: CaIRF1 is involved in the cellular IFN-I signaling pathway and plays an important role in the antiviral response.

Keywords: Antiviral characterization; CPV-2; Canine interferon regulatory factor 1; ISGs; ISRE.

MeSH terms

  • Animals
  • Antiviral Agents* / pharmacology
  • Dogs
  • Gene Expression Regulation
  • Interferon Regulatory Factor-1 / genetics
  • Interferon Regulatory Factor-1 / metabolism
  • Interferon-beta / genetics
  • Interferons* / metabolism
  • Mammals

Substances

  • Interferon Regulatory Factor-1
  • Antiviral Agents
  • Interferons
  • Interferon-beta