Takhampunya Ratree, Palmer Dupeh R, McClain Sasha, Barvir David A, Lynch Julia, Jarman Richard G, Thomas Stephen, Gibbons Robert V, Burgess Timothy H, Sun Peifang, Kamau Edwin, Putnak Robert, Zhang Chunlin
Division of Viral Diseases, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
Virus Res. 2009 Oct;145(1):31-8. doi: 10.1016/j.virusres.2009.05.016. Epub 2009 Jun 21.
Eighteen dengue viruses (DENVs) representing all four serotypes, isolated from pediatric patients at children's hospital, Queen Sirikit National Institute of Child Health, Bangkok, Thailand exhibiting a diverse spectrum of disease ranging from uncomplicated dengue fever (DF) to severe dengue hemorrhagic fever (DHF), were tested for their ability to attach to host cells, replicate and interfere with the IFNalpha signaling pathway by interfering with signal transducer and activator of transcription 1 (STAT-1) function. Although most isolates suppressed IFNalpha-induced STAT-1 phosphorylation, our results showed no difference between DENV strains associated with DF and those associated with DHF. However, the DHF isolates tended replicate to higher titers in dendritic cells (DCs) than the DF isolates, but this ability was independent of their cell-binding capability. Our results suggest that the emergence early in infection of viruses with a high degree of replication fitness may play an important role in DENV pathogenesis.
从泰国曼谷诗丽吉王后国家儿童健康研究所儿童医院的儿科患者中分离出代表所有四种血清型的18种登革病毒(DENV),这些患者表现出从单纯登革热(DF)到严重登革出血热(DHF)的多种疾病谱,对它们附着于宿主细胞、复制以及通过干扰信号转导和转录激活因子1(STAT-1)功能来干扰IFNα信号通路的能力进行了测试。尽管大多数分离株抑制了IFNα诱导的STAT-1磷酸化,但我们的结果显示,与DF相关的DENV毒株和与DHF相关的毒株之间没有差异。然而,DHF分离株在树突状细胞(DC)中的复制滴度往往高于DF分离株,但这种能力与其细胞结合能力无关。我们的结果表明,感染早期出现的具有高度复制适应性的病毒可能在DENV发病机制中起重要作用。