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A parapoxviral virion protein inhibits NF-κB signaling early in infection
Poxviruses have evolved unique proteins and mechanisms to counteract the nuclear factor κB (NF-κB) signaling pathway, which is an essential regulatory pathway of host innate immune responses. Here, we describe a NF-κB inhibitory virion protein of orf virus (ORFV), ORFV073, which functions very early...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5560748/ https://www.ncbi.nlm.nih.gov/pubmed/28787456 http://dx.doi.org/10.1371/journal.ppat.1006561 |
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author | Khatiwada, Sushil Delhon, Gustavo Nagendraprabhu, Ponnuraj Chaulagain, Sabal Luo, Shuhong Diel, Diego G. Flores, Eduardo F. Rock, Daniel L. |
author_facet | Khatiwada, Sushil Delhon, Gustavo Nagendraprabhu, Ponnuraj Chaulagain, Sabal Luo, Shuhong Diel, Diego G. Flores, Eduardo F. Rock, Daniel L. |
author_sort | Khatiwada, Sushil |
collection | PubMed |
description | Poxviruses have evolved unique proteins and mechanisms to counteract the nuclear factor κB (NF-κB) signaling pathway, which is an essential regulatory pathway of host innate immune responses. Here, we describe a NF-κB inhibitory virion protein of orf virus (ORFV), ORFV073, which functions very early in infected cells. Infection with ORFV073 gene deletion virus (OV-IA82Δ073) led to increased accumulation of NF-κB essential modulator (NEMO), marked phosphorylation of IκB kinase (IKK) subunits IKKα and IKKβ, IκBα and NF-κB subunit p65 (NF-κB-p65), and to early nuclear translocation of NF-κB-p65 in virus-infected cells (≤ 30 min post infection). Expression of ORFV073 alone was sufficient to inhibit TNFα induced activation of the NF-κB signaling in uninfected cells. Consistent with observed inhibition of IKK complex activation, ORFV073 interacted with the regulatory subunit of the IKK complex NEMO. Infection of sheep with OV-IA82Δ073 led to virus attenuation, indicating that ORFV073 is a virulence determinant in the natural host. Notably, ORFV073 represents the first poxviral virion-associated NF-κB inhibitor described, highlighting the significance of viral inhibition of NF-κB signaling very early in infection. |
format | Online Article Text |
id | pubmed-5560748 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-55607482017-08-25 A parapoxviral virion protein inhibits NF-κB signaling early in infection Khatiwada, Sushil Delhon, Gustavo Nagendraprabhu, Ponnuraj Chaulagain, Sabal Luo, Shuhong Diel, Diego G. Flores, Eduardo F. Rock, Daniel L. PLoS Pathog Research Article Poxviruses have evolved unique proteins and mechanisms to counteract the nuclear factor κB (NF-κB) signaling pathway, which is an essential regulatory pathway of host innate immune responses. Here, we describe a NF-κB inhibitory virion protein of orf virus (ORFV), ORFV073, which functions very early in infected cells. Infection with ORFV073 gene deletion virus (OV-IA82Δ073) led to increased accumulation of NF-κB essential modulator (NEMO), marked phosphorylation of IκB kinase (IKK) subunits IKKα and IKKβ, IκBα and NF-κB subunit p65 (NF-κB-p65), and to early nuclear translocation of NF-κB-p65 in virus-infected cells (≤ 30 min post infection). Expression of ORFV073 alone was sufficient to inhibit TNFα induced activation of the NF-κB signaling in uninfected cells. Consistent with observed inhibition of IKK complex activation, ORFV073 interacted with the regulatory subunit of the IKK complex NEMO. Infection of sheep with OV-IA82Δ073 led to virus attenuation, indicating that ORFV073 is a virulence determinant in the natural host. Notably, ORFV073 represents the first poxviral virion-associated NF-κB inhibitor described, highlighting the significance of viral inhibition of NF-κB signaling very early in infection. Public Library of Science 2017-08-07 /pmc/articles/PMC5560748/ /pubmed/28787456 http://dx.doi.org/10.1371/journal.ppat.1006561 Text en © 2017 Khatiwada et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Khatiwada, Sushil Delhon, Gustavo Nagendraprabhu, Ponnuraj Chaulagain, Sabal Luo, Shuhong Diel, Diego G. Flores, Eduardo F. Rock, Daniel L. A parapoxviral virion protein inhibits NF-κB signaling early in infection |
title | A parapoxviral virion protein inhibits NF-κB signaling early in infection |
title_full | A parapoxviral virion protein inhibits NF-κB signaling early in infection |
title_fullStr | A parapoxviral virion protein inhibits NF-κB signaling early in infection |
title_full_unstemmed | A parapoxviral virion protein inhibits NF-κB signaling early in infection |
title_short | A parapoxviral virion protein inhibits NF-κB signaling early in infection |
title_sort | parapoxviral virion protein inhibits nf-κb signaling early in infection |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5560748/ https://www.ncbi.nlm.nih.gov/pubmed/28787456 http://dx.doi.org/10.1371/journal.ppat.1006561 |
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