Announcement

Collapse
No announcement yet.

PLoS Pathog . Coronavirus nucleocapsid protein enhances the binding of p-PKCα to RACK1: Implications for inhibition of nucleocytoplasmic trafficking and suppression of the innate immune response

Collapse
X
 
  • Filter
  • Time
  • Show
Clear All
new posts

  • PLoS Pathog . Coronavirus nucleocapsid protein enhances the binding of p-PKCα to RACK1: Implications for inhibition of nucleocytoplasmic trafficking and suppression of the innate immune response

    PLoS Pathog


    . 2024 Nov 27;20(11):e1012097.
    doi: 10.1371/journal.ppat.1012097. Online ahead of print. Coronavirus nucleocapsid protein enhances the binding of p-PKCα to RACK1: Implications for inhibition of nucleocytoplasmic trafficking and suppression of the innate immune response

    Wenxiang Xue 1 , Hongyan Chu 1 , Jiehuang Wang 1 , Yingjie Sun 1 , Xusheng Qiu 1 , Cuiping Song 1 , Lei Tan 1 , Chan Ding 1 2 , Ying Liao 1



    AffiliationsFree article Abstract

    The hallmark of coronavirus infection lies in its ability to evade host immune defenses, a process intricately linked to the nuclear entry of transcription factors crucial for initiating the expression of antiviral genes. Central to this evasion strategy is the manipulation of the nucleocytoplasmic trafficking system, which serves as an effective target for the virus to modulate the expression of immune response-related genes. In this investigation, we discovered that infection with the infectious bronchitis virus (IBV) dynamically impedes the nuclear translocation of several transcription factors such as IRF3, STAT1, STAT2, NF-κB p65, and the p38 MAPK, leading to compromised transcriptional induction of key antiviral genes such as IFNβ, IFITM3, and IL-8. Further examination revealed that during the infection process, components of the nuclear pore complex (NPC), particularly FG-Nups (such as NUP62, NUP153, NUP42, and TPR), undergo cytosolic dispersion from the nuclear envelope; NUP62 undergoes phosphorylation, and NUP42 exhibits a mobility shift in size. These observations suggest a disruption in nucleocytoplasmic trafficking. Screening efforts identified the IBV nucleocapsid (N) protein as the agent responsible for the cytoplasmic distribution of FG-Nups, subsequently hindering the nuclear entry of transcription factors and suppressing the expression of antiviral genes. Interactome analysis further revealed that the IBV N protein interacts with the scaffold protein RACK1, facilitating the recruitment of activated protein kinase C alpha (p-PKCα) to RACK1 and relocating the p-PKCα-RACK1 complex to the cytoplasm. These observations are conserved across diverse coronaviruses N proteins. Concurrently, the presence of both RACK1 and PKCα/β proved essential for the phosphorylation and cytoplasmic dispersion of NUP62, the suppression of antiviral cytokine expression, and efficient virus replication. These findings unveil a novel, highly effective, and evolutionarily conserved mechanism.


Working...
X