猪繁殖与呼吸综合征病毒非结构蛋白1α（nsp1α）的N端锌指结构是其抑制NLRP3炎症小体活性所必需

doi:10.11843/j.issn.0366-6964.2015.11.016

Abstract

Abstract:

Porcine reproductive and respiratory syndrome（PRRS） is an important viral infectious disease in swine industry worldwide.The causative agent is porcine reproductive and respiratory syndrome virus（PRRSV），which can inhibit host innate and adaptive immune response，cause immunosuppression，and lead to persistent infection.So it is difficult to control and eradicate PRRS.As a critical part of innate immune，NLRP3 inflammasome plays an extremely important role in host anti-viral immunity.Previous studies have shown that PRRSV activated the NLRP3 inflammasome.However，whether there are components of PRRSV which suppress NLRP3 inflammasome remains unknown.Therefore，in the present study，we first reconstructed NLRP3 inflammasome through co-transfecting expression plasmids encoding NLRP3，ASC，procaspase-1，and pro-IL-1β in HEK293T cells which are deficient in endogenous inflammasomes.Then，HEK293T cells and porcine alveolar macrophages（PAMs） were transfected with expression plasmid encoding nsp1α of PRRSV.The results indicated that nsp1α can apparently block NLRP3 inflammasome activation.The further mutation experiments demonstrated that deletion or mutation of Zinc-Finger（ZF） domain in N-terminal of nsp1α fails to activate the NLRP3 inflammasome.Our study first demonstrated that nsp1α had the ability to suppress the NLRP3 inflammasome-mediated IL-1β secretion and ZF domain was essential for nsp1α to inhibit the IL-1β induction.Our study reveals a new mechanism that PRRSV antagonize host innate immune responses and may provide some insights into the research on molecular targets of anti-PRRSV drugs and prevention of PRRS.

CLC Number:

S852.659.6

WANG Chao，SHI Xi-bao，WANG Li，CHEN Jing，SI Chao-chao，WANG Ai-ping，DENG Rui-guang，ZHANG Gai-ping. The Zinc-Finger Domain is Essential for Porcine Reproductive and Respiratory Syndrome Virus Nonstructural Protein 1α（nsp1α） to Inhibit the NLRP3 Inflammasome[J]. ACTA VETERINARIA ET ZOOTECHNICA SINICA, 2015, 46(11): 2032-2039.

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The Zinc-Finger Domain is Essential for Porcine Reproductive and Respiratory Syndrome Virus Nonstructural Protein 1α（nsp1α） to Inhibit the NLRP3 Inflammasome

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