Type 2 BVDV Npro suppresses IFN-1 pathway signaling in bovine cells and augments BRSV replication

Abdulrahman A. Alkheraif, Christina L. Topliff, N R Jayagopala Reddy, Chandirasegaran Massilamany, Ruben O. Donis, Gregor Meyers, Kent M Eskridge, Clayton L Kelling

Research output: Contribution to journalArticle

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Abstract

Bovine viral diarrhea virus (BVDV) infection induces immunosuppression and in conjunction with bovine respiratory syncytial virus (BRSV) contributes to the bovine respiratory disease complex. Bovine turbinate cells were single or co-infected with type 2 BVDV wild-type (BVDV2-wt), its dysfunctional Npro mutant (BVDV2-E), and/or BRSV. BVDV2-E significantly up-regulated PKR, IRF-7, TBK-1, IRF-3, and IFN-β mRNAs based on real-time Q-RT-PCR. BRSV-infected cells expressed significantly up-regulated PKR, IRF-3, IRF-7, and IFN-β mRNAs, whereas BVDV2-wt, but not BVDV2-E, abolished this up-regulation in co-infection. No significant differences were observed in MAVS, NF-κB, and PIN-1 mRNAs. A dual-luciferase reporter assay showed that BVDV2-wt significantly increased NF-κB activity compared to BVDV2-E, while BVDV2-E significantly increased IFN-β activity compared to BVDV2-wt. The BRSV titer and RNA levels significantly increased in cells co-infected with BRSV/BVDV2-wt compared to cells co-infected with BRSV/BVDV2-E or infected with BRSV alone. This data supports the synergistic action of BVDV2-wt and BRSV inhibition of IFN-1.

Original languageEnglish (US)
Pages (from-to)123-134
Number of pages12
JournalVirology
Volume507
DOIs
StatePublished - Jul 1 2017

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Bovine viral diarrhea virus 2
Bovine respiratory syncytial virus
Virus Replication
Messenger RNA
Bovine Respiratory Disease Complex
Bovine Viral Diarrhea Viruses
Turbinates

Keywords

  • BRSV
  • BVDV2 N
  • Bovine respiratory disease complex
  • IFN-1 pathway signaling
  • Viral replication
  • mRNA

ASJC Scopus subject areas

  • Virology

Cite this

Type 2 BVDV Npro suppresses IFN-1 pathway signaling in bovine cells and augments BRSV replication. / Alkheraif, Abdulrahman A.; Topliff, Christina L.; Reddy, N R Jayagopala; Massilamany, Chandirasegaran; Donis, Ruben O.; Meyers, Gregor; Eskridge, Kent M; Kelling, Clayton L.

In: Virology, Vol. 507, 01.07.2017, p. 123-134.

Research output: Contribution to journalArticle

Alkheraif, Abdulrahman A. ; Topliff, Christina L. ; Reddy, N R Jayagopala ; Massilamany, Chandirasegaran ; Donis, Ruben O. ; Meyers, Gregor ; Eskridge, Kent M ; Kelling, Clayton L. / Type 2 BVDV Npro suppresses IFN-1 pathway signaling in bovine cells and augments BRSV replication. In: Virology. 2017 ; Vol. 507. pp. 123-134.
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AU - Alkheraif, Abdulrahman A.

AU - Topliff, Christina L.

AU - Reddy, N R Jayagopala

AU - Massilamany, Chandirasegaran

AU - Donis, Ruben O.

AU - Meyers, Gregor

AU - Eskridge, Kent M

AU - Kelling, Clayton L

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AB - Bovine viral diarrhea virus (BVDV) infection induces immunosuppression and in conjunction with bovine respiratory syncytial virus (BRSV) contributes to the bovine respiratory disease complex. Bovine turbinate cells were single or co-infected with type 2 BVDV wild-type (BVDV2-wt), its dysfunctional Npro mutant (BVDV2-E), and/or BRSV. BVDV2-E significantly up-regulated PKR, IRF-7, TBK-1, IRF-3, and IFN-β mRNAs based on real-time Q-RT-PCR. BRSV-infected cells expressed significantly up-regulated PKR, IRF-3, IRF-7, and IFN-β mRNAs, whereas BVDV2-wt, but not BVDV2-E, abolished this up-regulation in co-infection. No significant differences were observed in MAVS, NF-κB, and PIN-1 mRNAs. A dual-luciferase reporter assay showed that BVDV2-wt significantly increased NF-κB activity compared to BVDV2-E, while BVDV2-E significantly increased IFN-β activity compared to BVDV2-wt. The BRSV titer and RNA levels significantly increased in cells co-infected with BRSV/BVDV2-wt compared to cells co-infected with BRSV/BVDV2-E or infected with BRSV alone. This data supports the synergistic action of BVDV2-wt and BRSV inhibition of IFN-1.

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