Abstract

The transport of circovirus capsid protein into nucleus is essential for viral replication in infected cell. However, the role of nucleolar shuttle proteins during porcine circovirus 3 capsid protein (PCV3 Cap) import is still not understood. Here, we report a previously unidentified nucleolar localization signal (NoLS) of PCV3 Cap, which hijacks the nucleolar phosphoprotein nucleophosmin-1 (NPM1) to facilitate nucleolar localization of PCV3 Cap. The NoLS of PCV3 Cap and serine-48 residue of N-terminal oligomerization domain of NPM1 are essential for PCV3 Cap/NPM1 interaction. In addition, charge property of serine-48 residue of NPM1 is critical for nucleolar localization and interaction with PCV3 Cap. Taken together, our findings demonstrate for the first time that NPM1 interacts with PCV3 Cap and is responsible for its nucleolar localization.

Highlights

  • Viruses of genus Circovirus, in the family Circoviridae, have been detected in terrestrial, aquatic and avian species, including pigs, ducks, dogs, minks, rats, palm civets, geese, pigeons, canaries, parrots, and others [1,2,3,4,5,6,7,8]

  • The results indicate that the NPM1 is responsible for supporting the nucleolar localization of porcine circovirus type 3 (PCV3) capsid protein (Cap)

  • Two stretches of negatively charged amino acids in the primary structure of NPM1 are important because these motifs may potentially bind with positively-charged amino acid stretches in viral proteins, such as arginine-rich motif (ARM) and nuclear localization signal (NLS) [51]

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Summary

Introduction

Viruses of genus Circovirus, in the family Circoviridae, have been detected in terrestrial, aquatic and avian species, including pigs, ducks, dogs, minks, rats, palm civets, geese, pigeons, canaries, parrots, and others [1,2,3,4,5,6,7,8]. Two porcine circovirus (PCV) genotypes, PCV1 and PCV2, have been extensively studied [10, 11]. PCV1 is nonpathogenic to pigs and was identified in the porcine kidney cell line PK-15 [12, 13]. Retrospective research data have shown that PCV3 possesses high sequence homology to bat circovirus and that the earliest cases of PCV3 infection can be traced back to 1966 in China, suggesting that PCV3 may have been derived early from bats and gradually adapted to pigs [25].

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