Vol 57(2023) N 5 p. 876-884; DOI 10.1134/S0026893323050084
A.A. Latanova1*, K.K. Tuchinskaya2, E.S. Starodubova1, V.L. Karpov1
Hepatitis C Virus Nonstructural Protein 3 Increases Secretion of Interleukin-lbeta in HEK293T Cells with a Reconstructed NLRP3 Inflammasome1Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia
2Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products (Institute of Poliomyelitis) Russian Academy of Sciences, Moscow, 108811 Russia
Received - 2023-03-02; Revised - 2023-03-30; Accepted - 2023-03-31
The pathology of diseases arising from infections by viruses of Flaviviridae is largely determined by the development of systemic inflammation. The cytokines interleukin-1beta 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 pyrin domain-containing family 3) inflammasomes was detected in cells infected with Flaviviridae. Some nonstructural proteins of these viruses have been shown to be able to activate or to inhibit the NLRP3 inflammasome, in particular, through interaction with its components. In this study, a 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 NS1 proteins of the West Nile virus, NS3 of hepatitis C virus, or 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-1beta 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.
inflammasome, NLRP3, interleukin-1beta, tick-borne encephalitis virus, hepatitis C virus, West Nile virus, nonstructural proteins, Flaviviridae