Activation of Interleukin-1β Release by the Classical Swine Fever Virus Is Dependent on the NLRP3 Inflammasome, Which Affects Virus Growth in Monocytes

Abstract

Classical swine fever virus (CSFV) is a classic Flavivirus that causes the acute, febrile, and highly contagious disease known as classical swine fever (CSF). Inflammasomes are molecular platforms that trigger the maturation of proinflammatory cytokines to engage innate immune defenses that are induced upon cellular infection or stress. However, the relationship between the inflammasome and CSFV infection has not been thoroughly characterized. To understand the function of the inflammasome response to CSFV infection, we infected porcine peripheral blood monocytes (PBMCs) with CSFV. Our results indicated that CSFV infection induced both the generation of pro-interleukin-1β (pro-IL-1β) and its processing in monocytes, leading to the maturation and secretion of IL-1β through the activation of caspase 1. Moreover, CSFV infection in PBMCs induced the production and cleavage of gasdermin D (GSDMD), which is an inducer of pyroptosis. Additional studies showed that CSFV-induced IL-1β secretion was mediated by NLRP3 and that CSFV infection could sufficiently activate the assembly of the NLRP3 inflammasome in monocytes. These results revealed that CSFV infection inhibited the expression of NLRP3, and knockdown of NLRP3 enhanced the replication of CSFV. In conclusion, these findings demonstrate that the NLRP3 inflammasome plays an important role in the innate immune response to CSFV infection.

Apoptosis, Autophagy, and Pyroptosis: Immune Escape Strategies for Persistent Infection and Pathogenesis of Classical Swine Fever Virus

“…Pyroptosis is another important biological process of the antiviral immune response. The activation of NLRP3 inflammasome-mediated pyroptosis during CSFV infection may help explain why CSFV establishes a persistent infection in leukocytes [34,97]. Generally, apoptosis, autophagy, and pyroptosis can be observed throughout the occurrence and development of CSFV, and they play key roles in ultimate decisions of CSFV-infected cells' fates.…”

“…In viral infection, the assembly of the NLRP3 inflammasome is an important mechanism for caspase-1 activation, pyroptosis, and inflammation [26,88]. Studies by Fan et al showed that CSFV-infected porcine PBMCs caused the activation of an ATP-dependent K + ion channel and active NLRP3 inflammasome assembly, which led to caspase-1 activation and subsequent maturation and secretion of IL-1β, resulting in an inflammatory response [97]. Additional studies have showed that inhibiting the activation of the NLRP3 inflammasome can promote CSFV replication.…”

Newcastle disease virus RNA-induced IL-1β expression via the NLRP3/caspase-1 inflammasome

“…DNA viruses, such as poxvirus, herpes simplex virus, and adenovirus, can activate NLRP3 inflammasomes and promote IL-1β expression [19,20], while myxoma virus activates the NLRP3 inflammasome by inducing ROS and cathepsin B [21,22]. Many RNA viruses, such as infectious bronchitis virus, porcine reproductive and respiratory syndrome virus, and swine fever virus, induce IL-1β expression via the NLRP3 inflammasome [23][24][25]. The introduction of NLRP3 into ducks using a lentiviral expression system significantly increased the expression of NLRP3, IL-1β and IL-18 induced by E. coli and enhanced the degree of inflammation throughout the body [26].…”

Dual NDP52 Function in Persistent CSFV Infection

“…Co-and post-translational processing of the polypeptide by cellular and viral proteases yields 12 cleavage products, including four structural proteins (C, Erns, E1, and E2) and eight nonstructural proteins (N pro ,p7,NS2,NS3,NS4A,NS4B,NS5A,and NS5B) (Heinz-Jurgen et al, 1991). CSFV can infect several cells types, including immune cells, leading to cellular immunosuppression (Fan et al, 2018). However, CSFV infection does not cause typical pathological changes, and the underlying infection mechanisms remain unclear (Bensaude, 2004;Johns et al, 2009).…”