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A parapoxviral virion protein inhibits NF-κB signaling early in infection.
- Source :
-
PLoS Pathogens . 8/7/2017, Vol. 13 Issue 8, p1-29. 29p. - Publication Year :
- 2017
-
Abstract
- 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. [ABSTRACT FROM AUTHOR]
- Subjects :
- *VIRION
*POXVIRUSES
*PROTEINS
*PHOSPHORYLATION
*VIRUSES
Subjects
Details
- Language :
- English
- ISSN :
- 15537366
- Volume :
- 13
- Issue :
- 8
- Database :
- Academic Search Index
- Journal :
- PLoS Pathogens
- Publication Type :
- Academic Journal
- Accession number :
- 124496232
- Full Text :
- https://doi.org/10.1371/journal.ppat.1006561