Porcine DNAJB6 promotes PCV2 replication via enhancing the formation of autophagy in host cells

Cong Han,Dewen Tong,Qiao Chen,Lei Zhu,Qian Du,Xingchen Wu,Nannan Chen,Jiatong Yin,Yong Huang,Le Luo

doi:10.1186/s13567-020-00783-z

Cong Han, Dewen Tong + Show 8 more

Open Access

https://doi.org/10.1186/s13567-020-00783-z

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Abstract

Hsp40/DnaJ family proteins play important roles in the infection process of various viruses. Porcine DNAJB6 (pDNAJB6) is a major member of this family, but its role in modulating the replication of porcine circovirus type 2 (PCV2) is still unclear. In the present study, pDNAJB6 was found to be significantly upregulated by PCV2 infection, and confirmed to be interacted with PCV2 capsid (Cap) protein and co-localized at both cytoplasm and nucleus in the PCV2-infected cells. Knockout of pDNAJB6 significantly reduced the formation of autophagosomes in PCV2-infected cells or in the cells expressing Cap protein, whereas overexpression of pDNAJB6 showed an opposite effect. In addition, the domain mapping assay showed that the J domain of pDNAJB6 (amino acids (aa) 1–99) and the C terminus of Cap (162-234 aa) were required for the interaction of pDNAJB6 with Cap. Notably, the interaction of pDNAJB6 with Cap was very important to promoting the formation of autophagosomes induced by PCV2 infection or Cap expression and enhancing the replication of PCV2. Taken together, the results presented here show a novel function of pDNAJB6 in regulation of porcine circovirus replication that pDNAJB6 enhances the formation of autophagy to promote viral replication through interacting with viral capsid protein during PCV2 infection.

Highlights

Porcine circovirus associated diseases (PCVAD), caused by the porcine circovirus type 2 (PCV2), is one of the widespread infection diseases in the global swine industry
The results showed that Porcine DNAJB6 (pDNAJB6) expression significantly increased with the doses of PCV2 infection, suggesting that the expression level of pDNAJB6 is associated with viral loads (Figures 1D and E)
These results demonstrated that the expression of pDNAJB6 is upregulated by PCV2 infection

Summary

Introduction

Porcine circovirus associated diseases (PCVAD), caused by the porcine circovirus type 2 (PCV2), is one of the widespread infection diseases in the global swine industry. PCV2 belongs to the genus Circovirus within the family Circoviridae. The genome of PCV2 composed of 60-copies of capsid protein is a single-stranded, nosegmented and closed-circular DNA with 1.7 kb in size and 20 nm in diameter [1, 2]. The virus genome contains 11 open reading frames (ORFs) [3], and ORF1 encodes replication associated proteins (Rep, Rep’, Rep3a, Rep3b, Rep3c, NS515, NS672 and NS’) for the rolling circle replication of the genome [4]. ORF2 encodes another major structural protein, which is the unique capsid protein (Cap) and the important epitope of PCV2 [5]. ORF3 encodes the apoptotic associated protein, and ORF4 encodes antiapoptotic protein (ORFs) [3, 6, 7]

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