Studies On The Role Of Inflammation Cytokine And Inflammasomes In The Pathogenesis Of Hantavirus

This study first examined the level of a variety of inflammatory factors indifferent phase of HFRS patients’ plasma, and then use real-time quantitativePCR detected the mRNA levels of inflammatory cytokines in the HTNV76-118strain infected human umbilical vein endothelial cells(HUVEC). At the sametime, we detected the IL-1β levels in the HTNV infected HUVEC supernatant,and measured some of the mRNA levels of inflammasome compositionin theHTNV infected HUVEC. Thus to make clear whether the inflammation playrole in the pathogenic process of hantavirus infection.1. Detection of the inflammatory factors in HFRS patients’ peripheral bloodVEGF, sVEGFR1, sVEGFR2, sVE-cadherin, IL-1β, S1P and otherinflammatory related factors in141cases of HFRS patients’ plasma were detected. At the same time, samples of30healthy adults were used as controls.The test results showed that VEGF and sVE-cadherin levels were significantlyincreased at the severe phase of the disease. In contrast, the level of sVEGFR2showed opposite outcome, the higher the severity of the disease, the lower itscontent. The sVEGFR1was not detected in the healthy people, but itcould bemeasured it in the acute phase of HFRS patients’ plasma. Indicated sVEGFR1may take part in the pathogenesis of HFRS. Either IL-1β or S1P were notdetected it in the peripheral blood in both healthy adults and HFRS patients.2. Detection of the mRNA levels of inflammatory factorsin the HTNVinfected HUVECSome part of the factors were measured which were changed in the plasmain HFRS patients. The outcome showed S1P1, one of the receptors of S1P, waslower at the48h compared to the6h. VE-cadherin was also up-regulated at48hwhen compared to6h. This suggested that S1P1and VE-cadherin might take partin the pathogenesis of HFRS.3. Detection of IL-1β levelin HTNV infected HUVEC culture supernatantHantaan virus76-118strain were used to infected HUVEC, and the culturesupernatant IL-1β level were measured at different time post infection. Theresults showed that at very early time(6h), both active and60Co-inactived HTNVinduced high level of IL-1β secretion. While the mock group showed relativelylower level. But, as the infect time prolong, the outcome showed inversed results.IL-1β level were significantly decreased in both active and60Co-inactivedHTNV infected HUVEC compare to the mock group. This results indicated thatHTNV may suppress the inflammasome pathway during infection, and may notrelated to the replication of virus.4. Detection of inflammasome composition in HTNV infected HUVEC Real-time quantitative PCR results showed that both active and60Co-inactived HTNV induced HUVEC generate more IL-1β mRNA compare tomock group. Other inflammasome factors, such as NLRP3, caspase-1, etc.showed no significant change at any time point post infection. IL-18was notdetected in this experiment, while the level of IL-18binding protein(IL-18BP)changed the same as IL-1β. Western Blot results showed the levels of NLRP3and caspase-1were not changed in Hantavirus infected or normal HUVEC.These results suggested that the VEGF pathway and the inflammationfactors levels of HFRS patients were related to the severity of the diseaseprocess. Both results provides evidence that inflammation play a role in thepathogenesis of hantavirus. These results alsoindicated that Hantaan virus mightactivate the pathways of inflammasome at the early stage, and ight soonsuppress this response after endocytosis. But the very mechanisms of thisoutcome needs to be further explored.