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

PLoS Pathogens

Eduardo F. Flores¹  Ponnuraj Nagendraprabhu²  Sushil Khatiwada²  Daniel L. Rock²  Shuhong Luo²  Sabal Chaulagain²  Diego G. Diel²  Gustavo Delhon³ 

[1] Departamento de Medicina Veterinária Preventiva, Centro de Ciências Rurais, Universidade Federal de Santa Maria, Santa Maria, Rio Grande do Sul, Brazil;Department of Pathobiology, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America;School of Veterinary Medicine and Biomedical Science, Nebraska Center for Virology, University of Nebraska-Lincoln, Lincoln, Nebraska, United States of America

关键词: Transcription factors;    Sheep;    Signal inhibition;    Virions;    Phosphorylation;    Protein extraction;    Nitrocellulose;    Vaccinia virus;   

DOI  :  10.1371/journal.ppat.1006561

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY