Chen Lien-Cheng, Yeh Trai-Ming, Wu Huey-Nan, Lin Yi-Ying, Shyu Huey-Wen
Institute of Basic Medical Sciences, National Cheng Kung University, Taiwan, ROC.
J Infect. 2008 Feb;56(2):143-50. doi: 10.1016/j.jinf.2007.10.008.
Dengue hemorrhagic fever and dengue shock syndrome (DHF/DSS) are severe complications of secondary dengue virus (DV) infection. In the current study, we provide the first evidence of induction of cellular necrosis by DV type 2 (DV-2).
The epithelial cell line A549 can support replication of dengue virus as demonstrated by expression of viral NS1 antigen and virus plaque assay. DV-2 infection of cells induced cell death in approximately half of the cells that were actively infected. Using sodium 3'-[1-(phenylaminocarbonyl)-3, 4-tetrazolium]-bis(4-methoxy-6-nitro) benzene sulfonic acid hydrate [XTT]-based cell viability assays, we found that DV-2 infection at a multiplicity of infection (MOI) of 10 resulted in significant death of cells as well as high extracellular lactate dehydrogenase (LDH) activity and leakage of the high mobility group 1 (HMGB1) protein into the extracellular space.
These results suggest that HMGB1 may be a signal of tissue or cellular injury by DV-2, which in turn is likely to induce and/or enhance an immune reaction.
登革出血热和登革休克综合征（DHF/DSS）是继发性登革病毒（DV）感染的严重并发症。在本研究中，我们首次提供了2型登革病毒（DV-2）诱导细胞坏死的证据。
上皮细胞系A549能够支持登革病毒复制，病毒NS1抗原表达及病毒蚀斑试验均证实了这一点。DV-2感染细胞后，约一半被主动感染的细胞发生细胞死亡。使用基于3'-[1-(苯氨基羰基)-3,4-四氮唑]-双(4-甲氧基-6-硝基)苯磺酸水合物[XTT]的细胞活力检测方法，我们发现感染复数（MOI）为10时，DV-2感染导致细胞大量死亡，细胞外乳酸脱氢酶（LDH）活性升高，高迁移率族蛋白1（HMGB1）蛋白泄漏到细胞外空间。
这些结果表明，HMGB1可能是DV-2引起组织或细胞损伤的信号，进而可能诱导和/或增强免疫反应。
