Unknown

Dataset Information

0

A parapoxviral virion protein inhibits NF-κB signaling early in infection.


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.

SUBMITTER: Khatiwada S 

PROVIDER: S-EPMC5560748 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

altmetric image

Publications

A parapoxviral virion protein inhibits NF-κB signaling early in infection.

Khatiwada Sushil S   Delhon Gustavo G   Nagendraprabhu Ponnuraj P   Chaulagain Sabal S   Luo Shuhong S   Diel Diego G DG   Flores Eduardo F EF   Rock Daniel L DL  

PLoS pathogens 20170807 8


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  ...[more]

Similar Datasets

| S-EPMC5747488 | biostudies-literature
| S-EPMC4136316 | biostudies-literature
| S-EPMC5020088 | biostudies-literature
| S-EPMC8275679 | biostudies-literature
| S-EPMC5811242 | biostudies-literature
| S-EPMC4683373 | biostudies-other
| S-EPMC4525484 | biostudies-other
| S-EPMC5522097 | biostudies-literature
| S-EPMC3929693 | biostudies-literature
| S-EPMC8610585 | biostudies-literature