Dynamics of dengue disease severity determined by the interplay between viral genetics and serotype-specific immunity.
Dynamics of dengue disease severity determined by the interplay between viral genetics and serotype-specific immunity.
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DOI：
10.1126/scitranslmed.3003084
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发表时间：
2011-12-21
影响因子：
17.1
通讯作者：
Harris E
中科院分区：
文献类型：
--
作者：
OhAinle M;Balmaseda A;Macalalad AR;Tellez Y;Zody MC;Saborío S;Nuñez A;Lennon NJ;Birren BW;Gordon A;Henn MR;Harris E
登革热的迅速传播是一个世界性的公共卫生问题。在尼加拉瓜马那瓜的两项登革热临床研究中，我们观察到登革热病毒血清型 2 (DENV-2) 传播的几个流行季节中疾病严重程度突然增加。经过一段时间的交叉保护后，DENV-1 免疫力的减弱似乎会增加随后的 DENV-2 感染中患严重疾病的风险。严重程度的增加恰逢亚洲/美洲 DENV-2 NI-1 进化枝被新病毒进化枝 NI-2B 取代。对这两个分支的病毒分离株的体外分析以及患者血液样本中病毒血症的分析支持了相对于早期的流行季节，更适合的病毒的出现。此外，NI-1病毒分支在对DENV-1免疫的儿童中尤其具有更强的毒性，而DENV-3免疫与NI-2B感染中更严重的疾病相关。我们的数据表明，病毒遗传学和血清型特异性免疫的群体动态之间复杂的相互作用会增加严重登革热的风险。此外，这项工作提供了对病毒进化以及病毒适应性和毒力的病毒和免疫决定因素之间相互作用的见解。
The rapid spread of dengue is a worldwide public health problem. In two clinical studies of dengue in Managua, Nicaragua, we observed an abrupt increase in disease severity across several epidemic seasons of dengue virus serotype 2 (DENV-2) transmission. Waning DENV-1 immunity appeared to increase the risk of severe disease in subsequent DENV-2 infections after a period of cross-protection. The increase in severity coincided with replacement of the Asian/American DENV-2 NI-1 clade with a new virus clade, NI-2B. In vitro analyses of viral isolates from the two clades and analysis of viremia in patient blood samples support the emergence of a fitter virus in later, relative to earlier, epidemic seasons. In addition, the NI-1 clade of viruses was more virulent specifically in children who were immune to DENV-1, while DENV-3 immunity was associated with more severe disease among NI-2B infections. Our data demonstrate that the complex interaction between viral genetics and population dynamics of serotype-specific immunity contribute to the risk of severe dengue disease. Furthermore, this work provides insights into viral evolution and the interaction between viral and immunological determinants of viral fitness and virulence.