Paraoxonase-1 Facilitates PRRSV Replication by Interacting with Viral Nonstructural Protein-9 and Inhibiting Type I Interferon Pathway

Paraoxonase-1 (PON1), an esterase with specifically paraoxonase activity, has been proven to be involved in inflammation and infection. Porcine reproductive and respiratory syndrome virus (PRRSV) is still a major concern in pigs and causes severe economic losses to the swine industry worldwide. In t...

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Published in:Viruses 2022-05, Vol.14 (6), p.1203
Main Authors: Zhang, Lin, Pan, Yu, Xu, Yunfei, Zhang, Wenli, Ma, Wenjie, Ibrahim, Yassein M., Werid, Gebremeskel Mamu, Zhang, He, Xia, Changyou, Wei, Ping, Chen, Hongyan, Wang, Yue
Format: Article
Language:English
Subjects:
Alveoli
Animal diseases
DNA-directed RNA polymerase
Esterase
Experiments
Genomes
Hepatitis
Hogs
Infections
Infrared imaging systems
Interferon
Macrophages
Microscopy
Nsp9
Paraoxonase
paraoxonase-1
Plasmids
Proteins
PRRSV
Reagents
Replication
RNA polymerase
RNA-directed RNA polymerase
Severe acute respiratory syndrome coronavirus 2
Signal transduction
type I interferon pathway
Viruses
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Summary:Paraoxonase-1 (PON1), an esterase with specifically paraoxonase activity, has been proven to be involved in inflammation and infection. Porcine reproductive and respiratory syndrome virus (PRRSV) is still a major concern in pigs and causes severe economic losses to the swine industry worldwide. In this study, the role of PON1 was investigated in porcine alveolar macrophages (PAMs) during PRRSV infection. The results showed that PRRSV replication downregulated PON1, and the knockdown of PON1 significantly decreased PRRSV replication. Similarly, PON1 overexpression could enhance PRRSV replication. Interestingly, we observed that PON1 interacted with PRRSV nonstructural protein 9 (Nsp9), the RNA-dependent RNA polymerase, and the knockdown of PON1 lowered the RNA binding ability of Nsp9, suggesting that PON1 can facilitate Nsp9 function in viral replication. In addition, the knockdown of PON1 expression led to the amplification of type I interferon (IFN) genes and vice versa. In summary, our data demonstrate that PON1 facilitates PRRSV replication by interacting with Nsp9 and inhibiting the type I IFN signaling pathway. Hence, PON1 may be an additional component of the anti-PRRSV defenses.
ISSN:1999-4915
1999-4915
DOI:10.3390/v14061203