Nucleolin interacts with the rabbit hemorrhagic disease virus replicase RdRp, nonstructural proteins p16 and p23,

Jie Zhu1, Qiuhong Miao2, Hongyuan Guo1

  • 1Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, 200241, China.

Virologica Sinica
|March 2, 2022
PubMed

Insights

Rabbit hemorrhagic disease virus (RHDV) replication is poorly understood. This study identifies rabbit nucleolin (NCL) as essential for RHDV replication, acting as a crucial link between viral and host proteins.

Area of Science:

  • Virology
  • Molecular Biology
  • Cell Biology

Background:

  • Rabbit hemorrhagic disease virus (RHDV) belongs to the Caliciviridae family.
  • In vitro propagation challenges have hindered RHDV replication mechanism studies.
  • An RHDV replicon system offers a platform for investigating viral replication.

Purpose of the Study:

  • To identify host factors associated with the RHDV replicase.
  • To elucidate the role of host proteins in RHDV replication.
  • To understand the interaction network between viral replicase and host factors.

Main Methods:

  • Utilized an RHDV replicon system.
  • Employed two-step affinity purification to isolate RHDV replicase and associated proteins.
  • Performed gene overexpression and knockdown experiments in RK-13 cells.
  • Investigated protein-protein interactions using co-immunoprecipitation assays.

Main Results:

  • Identified rabbit nucleolin (NCL) as a key host factor interacting with RHDV replicase.
  • NCL mediates interactions between the viral replicase and other RNA-dependent RNA polymerase (RdRp)-related host proteins.
  • NCL overexpression enhanced RHDV replication, while NCL knockdown severely impaired it.
  • NCL directly interacts with RHDV RdRp, p16, and p23, and is crucial for binding of RdRp to other host factors.

Conclusions:

  • Host protein NCL is essential for RHDV replication.
  • NCL functions as a physical linker, connecting the viral replicase to host proteins.
  • Understanding NCL's role provides insights into RHDV replication strategies.

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