Rico-Hesse R, Harrison L M, Nisalak A, Vaughn D W, Kalayanarooj S, Green S, Rothman A L, Ennis F A
Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Am J Trop Med Hyg. 1998 Jan;58(1):96-101. doi: 10.4269/ajtmh.1998.58.96.
Dengue is a mosquito-borne viral infection that in recent years has become a major international public health concern. Dengue hemorrhagic fever (DHF), first recognized in Southeast Asia in the 1950s, is today a leading cause of childhood death in many countries. The pathogenesis of this illness is poorly understood, mainly because there are no laboratory or animal models of disease. We have studied the genetic relationships of dengue viruses of serotype 2, one of four antigenically distinct dengue virus groups, to determine if viruses obtained from cases of less severe dengue fever (DF) have distinct evolutionary origins from those obtained from DHF cases. A very large number (73) of virus samples from patients with DF or DHF in two locations in Thailand (Bangkok and Kamphaeng Phet) were compared by sequence analysis of 240 nucleotides from the envelope/nonstructural protein 1 (E/NS1) gene junction of the viral genome. Phylogenetic trees generated with these data have been shown to reflect long-term evolutionary relationships among strains. The results suggest that 1) many different virus variants may circulate simultaneously in Thailand, thus reflecting the quasispecies nature of these RNA viruses, in spite of population immunity; 2) viruses belonging to two previously distinct genotypic groups have been isolated from both DF and DHF cases, supporting the view that they arose from a common progenitor and share the potential to cause severe disease; and 3) viruses associated with the potential to cause DHF segregate into what is now one, large genotypic group and they have evolved independently in Southeast Asia for some time.
登革热是一种由蚊子传播的病毒感染，近年来已成为国际公共卫生的一大关注点。登革出血热（DHF）于20世纪50年代在东南亚首次被确认，如今在许多国家是儿童死亡的主要原因。这种疾病的发病机制尚不清楚，主要是因为没有疾病的实验室模型或动物模型。我们研究了血清型2登革病毒的遗传关系，血清型2是四种抗原性不同的登革病毒组之一，以确定从症状较轻的登革热（DF）病例中分离出的病毒与从DHF病例中分离出的病毒是否有不同的进化起源。通过对病毒基因组包膜/非结构蛋白1（E/NS1）基因连接处240个核苷酸进行序列分析，比较了来自泰国两个地区（曼谷和甘烹碧）的大量（73个）DF或DHF患者的病毒样本。用这些数据生成的系统发育树已被证明能反映毒株之间的长期进化关系。结果表明：1）尽管有群体免疫，但许多不同的病毒变体可能在泰国同时传播，从而反映出这些RNA病毒的准种性质；2）从DF和DHF病例中都分离出了属于两个先前不同基因型组的病毒，这支持了它们起源于共同祖先并具有引发严重疾病潜力的观点；3）与引发DHF潜力相关的病毒分离成现在的一个大基因型组，并且它们在东南亚已经独立进化了一段时间。
