Abstract

Porcine circovirus type 4 (PCV4) is an emerging etiological agent which was first detected in 2019. The nucleolar localization signal (NoLS) of PCV4 Cap protein and its binding host cellular proteins are still not elucidated. In the present study, we discovered a distinct novel NoLS of PCV4 Cap, which bound to the nucleolar phosphoprotein nucleophosmin-1 (NPM1). The NoLS of PCV4 Cap and serine-48 residue at the N-terminal oligomerization domain of NPM1 were necessary for PCV4 Cap/NPM1 interaction. Furthermore, the charge property of serine residue at position 48 of the NPM1 was crucial for its oligomerization and interaction with PCV4 Cap. In summary, our findings show for the first time that the PCV4 Cap NoLS and the NPM1 oligomerization determine the interaction of Cap/NPM1.

Highlights

  • Porcine circoviruses (PCVs), which are small non-enveloped viruses within the genus Circovirus of the family Circoviridae, have a circular single-stranded DNA genome with a size of about 1.7–2.0 kb in length (Breitbart et al, 2017)

  • We reported that the nucleolar localization signal (NoLS) of Porcine circovirus type 4 (PCV4) Cap and serine-48 residue of the NPM1 N-terminal oligomerization domain are required for PCV4 Cap/NPM1 interaction

  • The results indicated that amino acid residues 1–37 at the N-terminus of PCV4 Cap was a NoLS and played a prominent role in nucleolar localization

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Summary

Introduction

Porcine circoviruses (PCVs), which are small non-enveloped viruses within the genus Circovirus of the family Circoviridae, have a circular single-stranded DNA (ssDNA) genome with a size of about 1.7–2.0 kb in length (Breitbart et al, 2017). PCV3 was first detected in the United States in 2015 with metagenomic sequencing and is associated with various clinical diseases, including porcine dermatitis and nephropathy syndrome (PDNS), reproductive failure, respiratory disease, and diarrhea (Phan et al, 2016; Palinski et al, 2017; Jiang et al, 2019). PCV4, a previously unidentified PCV, which was first detected in Hunan province, China, in 2019, was considered to be related to serious clinical signs, including respiratory distress and PDNS (Zhang et al, 2019). PCV4 has been discovered in some other provinces in China (Sun et al, 2020; Chen et al, 2021; Ha et al, 2021; Tian et al, 2021), PCV4 Capsid Interaction With Nucleophosmin-1 demonstrating that PCV4 is probably prevalent in Chinese pig farms. PCV4 was reported in South Korea but was not discovered in Italy and Spain (Franzo et al, 2020; Nguyen et al, 2021)

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