Porcine reproductive and respiratory syndrome virus non-structural protein 1 suppresses tumor necrosis factor-alpha promoter activation by inhibiting NF-κB and Sp1

Sakthivel Subramaniam; Byungjoon Kwon; Lalit K. Beura; Charles A. Kuszynski; Asit K. Pattnaik; Fernando A. Osorio

doi:10.1016/j.virol.2010.07.016

Porcine reproductive and respiratory syndrome virus non-structural protein 1 suppresses tumor necrosis factor-alpha promoter activation by inhibiting NF-κB and Sp1

Sakthivel Subramaniam
, Byungjoon Kwon
, Lalit K. Beura
, Charles A. Kuszynski
, Asit K. Pattnaik
, Fernando A. Osorio

Microbiology

Research output: Contribution to journal › Article › peer-review

72 Scopus citations

Abstract

The objective of this study was to identify porcine reproductive and respiratory syndrome virus (PRRSV)-encoded proteins that are responsible for the inhibition of TNF-α expression and the mechanism(s) involved in this phenomenon. Using a TNF-α promoter reporter system, the non-structural protein 1 (Nsp1) was found to strongly suppress the TNF-α promoter activity. Such inhibition takes place especially at the promoter's proximal region. Both Nsp1α and Nsp1β, the two proteolytic fragments of Nsp1, were shown to be involved in TNF-α promoter suppression. Furthermore, using reporter plasmids specific for transcription factors (TFs) that bind to TNF-α promoter, Nsp1α and Nsp1β were demonstrated to inhibit the activity of the TFs that bind CRE-κB₃ and Sp1 elements respectively. Subsequent analyses showed that Nsp1α moderately inhibits NF-κB activation and that Nsp1β completely abrogates the Sp1 transactivation. These findings reveal one of the important mechanisms underlying the innate immune evasion by PRRSV during infection.

Original language	English (US)
Pages (from-to)	270-279
Number of pages	10
Journal	Virology
Volume	406
Issue number	2
DOIs	https://doi.org/10.1016/j.virol.2010.07.016
State	Published - Oct 2010

Bibliographical note

Funding Information:
In order to prepare primary cells ex vivo , blood was collected from donor pigs by following protocols approved by the Institutional Animal Care and Use Committee of the University of Nebraska-Lincoln under the protocol IACUC No.07-10-048C. This research has been supported by a grant from the USDA NRICGP (project 2008-00903 USDA-NRICGP).

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Innate immune evasion
NF-κB
PRRSV
Promoter suppression
Sp1
Tumor necrosis factor-α

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10.1016/j.virol.2010.07.016

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title = "Porcine reproductive and respiratory syndrome virus non-structural protein 1 suppresses tumor necrosis factor-alpha promoter activation by inhibiting NF-κB and Sp1",

abstract = "The objective of this study was to identify porcine reproductive and respiratory syndrome virus (PRRSV)-encoded proteins that are responsible for the inhibition of TNF-α expression and the mechanism(s) involved in this phenomenon. Using a TNF-α promoter reporter system, the non-structural protein 1 (Nsp1) was found to strongly suppress the TNF-α promoter activity. Such inhibition takes place especially at the promoter's proximal region. Both Nsp1α and Nsp1β, the two proteolytic fragments of Nsp1, were shown to be involved in TNF-α promoter suppression. Furthermore, using reporter plasmids specific for transcription factors (TFs) that bind to TNF-α promoter, Nsp1α and Nsp1β were demonstrated to inhibit the activity of the TFs that bind CRE-κB3 and Sp1 elements respectively. Subsequent analyses showed that Nsp1α moderately inhibits NF-κB activation and that Nsp1β completely abrogates the Sp1 transactivation. These findings reveal one of the important mechanisms underlying the innate immune evasion by PRRSV during infection.",

keywords = "Innate immune evasion, NF-κB, PRRSV, Promoter suppression, Sp1, Tumor necrosis factor-α",

author = "Sakthivel Subramaniam and Byungjoon Kwon and Beura, \{Lalit K.\} and Kuszynski, \{Charles A.\} and Pattnaik, \{Asit K.\} and Osorio, \{Fernando A.\}",

note = "Funding Information: In order to prepare primary cells ex vivo , blood was collected from donor pigs by following protocols approved by the Institutional Animal Care and Use Committee of the University of Nebraska-Lincoln under the protocol IACUC No.07-10-048C. This research has been supported by a grant from the USDA NRICGP (project 2008-00903 USDA-NRICGP). ",

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doi = "10.1016/j.virol.2010.07.016",

language = "English (US)",

volume = "406",

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journal = "Virology",

issn = "0042-6822",

publisher = "Academic Press Inc.",

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AU - Subramaniam, Sakthivel

AU - Kwon, Byungjoon

AU - Beura, Lalit K.

AU - Kuszynski, Charles A.

AU - Pattnaik, Asit K.

AU - Osorio, Fernando A.

N1 - Funding Information: In order to prepare primary cells ex vivo , blood was collected from donor pigs by following protocols approved by the Institutional Animal Care and Use Committee of the University of Nebraska-Lincoln under the protocol IACUC No.07-10-048C. This research has been supported by a grant from the USDA NRICGP (project 2008-00903 USDA-NRICGP).

PY - 2010/10

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N2 - The objective of this study was to identify porcine reproductive and respiratory syndrome virus (PRRSV)-encoded proteins that are responsible for the inhibition of TNF-α expression and the mechanism(s) involved in this phenomenon. Using a TNF-α promoter reporter system, the non-structural protein 1 (Nsp1) was found to strongly suppress the TNF-α promoter activity. Such inhibition takes place especially at the promoter's proximal region. Both Nsp1α and Nsp1β, the two proteolytic fragments of Nsp1, were shown to be involved in TNF-α promoter suppression. Furthermore, using reporter plasmids specific for transcription factors (TFs) that bind to TNF-α promoter, Nsp1α and Nsp1β were demonstrated to inhibit the activity of the TFs that bind CRE-κB3 and Sp1 elements respectively. Subsequent analyses showed that Nsp1α moderately inhibits NF-κB activation and that Nsp1β completely abrogates the Sp1 transactivation. These findings reveal one of the important mechanisms underlying the innate immune evasion by PRRSV during infection.

AB - The objective of this study was to identify porcine reproductive and respiratory syndrome virus (PRRSV)-encoded proteins that are responsible for the inhibition of TNF-α expression and the mechanism(s) involved in this phenomenon. Using a TNF-α promoter reporter system, the non-structural protein 1 (Nsp1) was found to strongly suppress the TNF-α promoter activity. Such inhibition takes place especially at the promoter's proximal region. Both Nsp1α and Nsp1β, the two proteolytic fragments of Nsp1, were shown to be involved in TNF-α promoter suppression. Furthermore, using reporter plasmids specific for transcription factors (TFs) that bind to TNF-α promoter, Nsp1α and Nsp1β were demonstrated to inhibit the activity of the TFs that bind CRE-κB3 and Sp1 elements respectively. Subsequent analyses showed that Nsp1α moderately inhibits NF-κB activation and that Nsp1β completely abrogates the Sp1 transactivation. These findings reveal one of the important mechanisms underlying the innate immune evasion by PRRSV during infection.

KW - Innate immune evasion

KW - NF-κB

KW - PRRSV

KW - Promoter suppression

KW - Sp1

KW - Tumor necrosis factor-α

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Porcine reproductive and respiratory syndrome virus non-structural protein 1 suppresses tumor necrosis factor-alpha promoter activation by inhibiting NF-κB and Sp1

Abstract

Bibliographical note

UN SDGs

Keywords

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