Abstract

Interferon regulatory factor 1 (IRF1), as an important transcription factor, is abundantly induced upon virus infections and participates in host antiviral immune responses. However, the roles of porcine IRF1 (poIRF1) in host antiviral defense remain poorly understood. In this study, we determined that poIRF1 was upregulated upon infection with viruses and distributed in nucleus in porcine PK-15 cells. Subsequently, we tested the antiviral activities of poIRF1 against several swine viruses in cells. Overexpression of poIRF1 can efficiently suppress the replication of viruses, and knockdown of poIRF1 promotes moderately viral replication. Interestingly, overexpression of poIRF1 enhances dsRNA-induced IFN-β and IFN-stimulated response element (ISRE) promoter activation, whereas knockdown of poIRF1 cannot significantly affect the activation of IFN-β promoter induced by RNA viruses. This study suggests that poIRF1 plays a significant role in cellular antiviral response against swine viruses, but might be dispensable for IFN-β induction triggered by RNA viruses in PK-15 cells. Given these results, poIRF1 plays potential roles in cellular antiviral responses against swine viruses.

Highlights

  • Virus infection and subsequent replication poses a significant threat to the host immune system

  • When a virus is invading a cell, cellular pattern recognition receptors (PRRs) can recognize viral nucleic acids, and transmit signals to downstream adaptors, which eventually results in the activation of transcription factors of IFN regulatory factor (IRF) family, primarily including IRF3 and/or IRF7, to induce the expression of type I IFN [1]

  • The results indicated that overexpression of porcine IRF1 (poIRF1) potently inhibits virutos preoTpIRoliFcda1ett(iesoirn-mI.RinFe1)wwhaesthtrearnesnfdecotgeednionutos poIRF1 expression PK-15 cells with a affects viral replication, non-targeting Small interfering RNAs (siRNA) as siRNA targeting control

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Summary

Introduction

Virus infection and subsequent replication poses a significant threat to the host immune system. As the first member of IRF family, IRF1 is constitutively expressed in most cell types and is dramatically induced upon viral infection, treatment with dsRNA or IFN stimulation [3,4,5]. Our study revealed that the absence of IRF1 did not clearly affect the induction of IFN-β in PK-15 cells in response to RNA virus infections but impaired the activation of ISRE, indicating that the antiviral phenotype of poIRF1 was not a consequence of IFN-β production and may have arisen directly through ISGs expression. Our study demonstrated that poIRF1 as an interferon-induced protein plays a significant role in cellular antiviral responses against four kinds of swine viruses, but might be dispensable for IFN-β induction triggered by RNA viruses in PK-15 cells. PoIRF1 plays potential roles in cellular antiviral responses against swine viruses

Materials and Methods
Cells and Viruses
Western Blot
Generation of Stable Cell Lines
Antiviral Activity Evaluation
Findings
Luciferase Reporter Assay

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