Contribution of DEAD-Box RNA Helicase 21 to the Nucleolar Localization of Porcine Circovirus Type 4 Capsid Protein.

Jianwei Zhou,Changzhe Liu,Xiaoyu Yang,Lei Hou,Yuexia Wang,Yongxia Wang,Yongyan Shi,Xufei Feng,Jue Liu,Yonghui Qiu

doi:10.3389/fmicb.2022.802740

Abstract

Porcine circovirus type 4 (PCV4) is a newly emerging pathogen which might be associated with diverse clinical signs, including respiratory and gastrointestinal distress, dermatitis, and various systemic inflammations. The host cellular proteins binding to PCV4 capsid (Cap) protein are still not clear. Herein, we found that the PCV4 Cap mediated translocation of DEAD-box RNA helicase 21 (DDX21) to the cytoplasm from the nucleolus and further verified that the nucleolar localization signal (NoLS) of the PCV4 Cap bound directly to the DDX21. The NoLS of PCV4 Cap and 763GSRSNRFQNK772 residues at the C-terminal domain (CTD) of DDX21 were required for this PCV4 Cap/DDX21 interaction. Further studies indicated that the PCV4 Cap NoLS exploited DDX21 to facilitate its nucleolar localization. In summary, our results firstly demonstrated that DDX21 binds directly to the NoLS of the PCV4 Cap thereby contributing to the nucleolar localization of the PCV4 Cap protein.

Highlights

Porcine circoviruses (PCVs) belong to non-enveloped viruses containing single-stranded circular DNA genomes (∼1.7–2.0 kb) within genus Circovirus in the family Circoviridae (Breitbart et al, 2017)
We found that DEAD-box RNA helicase 21 (DDX21) traffics to the cytoplasm from the nucleolus induced by the Porcine circovirus type 4 (PCV4) Cap overexpression and the nucleolar localization signal (NoLS) of the PCV4 Cap and 763GSRSNRFQNK772 residues at the C-terminal domain (CTD) of DDX21 are essential for the PCV4 Cap/DDX21 interaction
DDX21 is known to be a nucleolar protein within the DEAD-box RNA helicase family, its localization can be altered upon certain types of stimulation (Dong et al, 2016)

Summary

Introduction

Porcine circoviruses (PCVs) belong to non-enveloped viruses containing single-stranded circular DNA genomes (∼1.7–2.0 kb) within genus Circovirus in the family Circoviridae (Breitbart et al, 2017). Four genotypes of circoviruses have been detected in pigs (Zhang et al, 2019; Oh and Chae, 2020; Opriessnig et al, 2020). PCV1 is non-pathogenic, while PCV2 is the main pathogen of porcine circovirus-associated diseases (PCVAD) (Tischer et al, 1982; Allan et al, 1998). PCV4, a novel PCV, which was first reported in Hunan province, China in 2019, was related to clinical symptoms, such as respiratory distress and porcine dermatitis and nephropathy syndrome (PDNS) (Zhang et al, 2019). PCV4 was detected in other pig-rearing provinces in China as well (Sun et al, 2020; Tian et al, 2020; Chen et al, 2021; Ha et al, 2021), indicating that PCV4 is probably prevalent in Chinese swine farms. PCV4 was found in South Korea but not detected in Italy and Spain (Franzo et al, 2020; Nguyen et al, 2021)

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Conclusion