A parapoxviral virion protein inhibits NF-κB signaling early in infection.
PLoS Pathog
; 13(8): e1006561, 2017 Aug.
Article
in En
| MEDLINE
| ID: mdl-28787456
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 IKKß, 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Orf virus
/
Virion
/
NF-kappa B
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Ecthyma, Contagious
/
Immune Evasion
Limits:
Animals
/
Humans
Language:
En
Journal:
PLoS Pathog
Year:
2017
Document type:
Article
Affiliation country:
United States