Both Nsp1β and Nsp11 are responsible for differential TNF-α production induced by porcine reproductive and respiratory syndrome virus strains with different pathogenicity in vitro

Porcine reproductive and respiratory syndrome virus (PRRSV) has been recognized to be one of the most important pathogens severely affecting global swine industry. An increasingly number of studies have paid much attention to the diverse roles of its nonstructural proteins (Naps) in regulating the innate immune response of host upon PRRSV infection. In the present study, we first discovered that highly pathogenic PRRSV (HP-PRRSV) and low pathogenic PRRSV (LP-PRRSV) infection exhibited a differential TNF-alpha expression in pulmonary alveolar macrophages (PAMs), showing that HP-PRRSV infection induces lower TNF-alpha production at protein level in PAMs, compared with LP-PRRSV. Next, HP-PRRSV was confirmed to strongly suppress TNF-alpha production by inhibiting ERK signaling pathway. Finally, both Nsp1 beta and Nsp11 were demonstrated to be responsible for the inhibitory effect on TNF-alpha production induced by HP-PRRSV and the differential TNF-alpha production in PAMs. These findings contribute to the understanding of the pathogenesis of the Chinese HP-PRRSV. (C) 2015 Elsevier B.V. All rights reserved.