| Summary: | 碩士 === 國防醫學院 === 微生物及免疫學研究所 === 87 === Flavivirus genome is a single-stranded, positive-sense RNA of appopximately 11 kb. Theoretically, an RNA virus such as flavivirus completes its life cycle in the cytoplasm of host cells, then it is interesting to know whether nuclear factor is involved in this virus replication. The nuclear factor NF-B forms a complex with its inhibitor I-B and is sequestered in the cytoplasm. Sodium salicylate (NaSal) has been recently demonstrated to prevent the phosphorylation and subsequent degradation of I-B, then the NF-B remains in the cytoplasm in an inactivated form. In a previous study, apoptosis of a hepatoma cell line (HepG2) by dengue virus type I (DEN-1), a member of flaviviruses, is related to the activation of NF-BIn this thesis, we demonstrate that NaSal could inhibit dengue virus type II (DEN-2) replication in a liver cell line (Chang liver). Over expressing the dominant negative mutant of I-B decreased the apoptosis induced by DEN-2 infection, indicating that the death of liver cells by DEN-2 infection involves NF-B activation. Our previous data have also shown that NaSal delayed the apoptosis induced by Japanese encephalitis virus (JEV), also a member of flaviviruses and DEN-2 infection, as well as virus replication in BHK-21 (baby hamster kidney cell) and N18 (mouse neuroblastoma cell) cells. Whereas it appeared in these two non-liver cells that the inhibition effect did not go through blocking the activation of NF-B. In this study, we further demonstrate that NaSal inhibited the apoptosis induced by flavivirus replication probably due to that NaSal could inhibit the decrease of mitochondria membrane potential resulted from flavivirus infection. Furthermore inhibition of p38 MAPK (mitogen activated protein kinase) activation could partially reverse the inhibition of flavivirus replication by NaSal. Besides, NaSal could inhibit the activation of cyclic AMP-dependent protein kinase in BHK-21 and N18 cells. Overall, it appears that the life cycle of flavivirus replication has a closed and diverse relationship with the activation of intracellular signal transduction.
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