Hepatitis C Virus Nonstructural Protein 3 Increases Secretion of Interleukin-1beta in HEK293T Cells with Reconstructed NLRP3 Inflammasome

Abstract

Infections caused by Flaviviridae pose a threat in the modern world. The pathology of diseases arising from these infections is largely determined by the development of systemic inflammation. The cytokines interleukin-1 beta and interleukin-18 play a key role in triggering inflammation. Their secretion from cells, in its turn, is induced upon activation of inflammasomes. Activation of NLRP3 (NLR family pyrin domain-containing 3) inflammasomes was detected in the cells infected with Flaviviridae. Some nonstructural proteins of these viruses have been shown to be able to activate or inhibit the NLRP3 inflammasome, in particular, through interaction with its components. In this study, the functional NLRP3 inflammasome was reconstructed in human HEK293T cells and the effect of some nonstructural proteins of individual Flaviviridae viruses on it was studied. This model did not reveal any impact of nonstructural proteins NS1 of West Nile virus, NS3 of hepatitis C virus, NS5 of tick-borne encephalitis virus on the inflammasome components content. At the same time, in the presence of the NS1 of the West Nile virus and NS5 of the tick-borne encephalitis virus, the level of secretion of interleukin-1 beta did not change, whereas in the presence of the NS3 protein of the hepatitis C virus, it increased by 1.5 times. Thus, NS3 can be considered as one of the factors of NLRP3 inflammasome activation and inflammatory pathogenesis in chronic hepatitis C virus infection.