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...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2017-08-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1006561 |
| _version_ | 1818589570108751872 |
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| author | Sushil Khatiwada Gustavo Delhon Ponnuraj Nagendraprabhu Sabal Chaulagain Shuhong Luo Diego G Diel Eduardo F Flores Daniel L Rock |
| author_facet | Sushil Khatiwada Gustavo Delhon Ponnuraj Nagendraprabhu Sabal Chaulagain Shuhong Luo Diego G Diel Eduardo F Flores Daniel L Rock |
| author_sort | Sushil Khatiwada |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-16T09:42:45Z |
| format | Article |
| id | doaj.art-b1d0abe032294ef9942f4da6008c9c56 |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-16T09:42:45Z |
| publishDate | 2017-08-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-b1d0abe032294ef9942f4da6008c9c562022-12-21T22:36:13ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742017-08-01138e100656110.1371/journal.ppat.1006561A parapoxviral virion protein inhibits NF-κB signaling early in infection.Sushil KhatiwadaGustavo DelhonPonnuraj NagendraprabhuSabal ChaulagainShuhong LuoDiego G DielEduardo F FloresDaniel L RockPoxviruses 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.https://doi.org/10.1371/journal.ppat.1006561 |
| spellingShingle | Sushil Khatiwada Gustavo Delhon Ponnuraj Nagendraprabhu Sabal Chaulagain Shuhong Luo Diego G Diel Eduardo F Flores Daniel L Rock A parapoxviral virion protein inhibits NF-κB signaling early in infection. PLoS Pathogens |
| 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 |
| url | https://doi.org/10.1371/journal.ppat.1006561 |
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