Mitochondrial Localization Signal of Porcine Circovirus Type 2 Capsid Protein Plays a Critical Role in Cap-Induced Apoptosis.

Wanting Yu,Luhua Zhang,Yang Zhan,Yujie Sun,Naidong Wang,Yuao Sun,Qing He,Yi Yang,Chaoying Sun,Tian Dong

doi:10.3390/vetsci8110272

Abstract

Porcine circovirus 2 (PCV2), considered one of the most globally important porcine pathogens, causes postweaning multisystemic wasting syndrome (PMWS). This virus is localized in the mitochondria in pigs with PMWS. Here, we identified, for the first time, a mitochondrial localization signal (MLS) in the PCV2 capsid protein (Cap) at the N-terminus. PK-15 cells showed colocalization of the MLS-EGFP fusion protein with mitochondria. Since the PCV2 Cap also contained a nuclear localization signal (NLS) that mediated entry into the nucleus, we inferred that the subcellular localization of the PCV2 Cap is inherently complex and dependent on the viral life cycle. Furthermore, we also determined that deletion of the MLS attenuated Cap-induced apoptosis. More importantly, the MLS was essential for PCV2 replication, as absence of the MLS resulted in failure of virus rescue from cells infected with infectious clone DNA. In conclusion, the MLS of the PCV2 Cap plays critical roles in Cap-induced apoptosis, and MLS deletion of Cap is lethal for virus rescue.

Highlights

Porcine circovirus 2 (PCV2) is the primary pathogen causing postweaning multisystemic wasting syndrome (PMWS), an emerging swine disease first discovered in WesternCanada approximately 30 years ago [1,2,3]
We identified a mitochondrial localization signal (MLS) in the PCV2 capsid protein (Cap) protein, which demonstrated the critical role of the newly identified MLS in Cap-induced apoptosis, and determined that infectious cloned DNA missing the MLS was incapable of virus rescue, demonstrating that MLS deletion of Cap is lethal for virus rescue
Mitochondria are involved in a variety of cellular metabolic processes, including proliferation, differentiation, apoptosis, senescence, and calcium homeostasis

Summary

Introduction

Porcine circovirus 2 (PCV2) is the primary pathogen causing postweaning multisystemic wasting syndrome (PMWS), an emerging swine disease first discovered in Western. Canada approximately 30 years ago [1,2,3]. PCV, the smallest virus to infect mammals, belongs to the family Circoviridae and the genus Circovirus. Four genotypes of PCV have been identified [1]. In addition to pathogenic PCV2, more recently, PCV3 and PCV4 have been identified and are considered to be pathogenic, PCV1 is not pathogenic [4,5]. PCV2 is one of the most important pathogens in the swine industry, due to its pathogenicity and continuous evolution [6]. PCV2 is a non-enveloped virus that packages a 1.7 kb single-stranded and circular

Methods

Results

Conclusion