PATHOGENESIS OF DENGUE - CHALLENGES TO MOLECULAR-BIOLOGY
PATHOGENESIS OF DENGUE - CHALLENGES TO MOLECULAR-BIOLOGY
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DOI：
10.1126/science.3277268
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发表时间：
1988-01-29
期刊：
影响因子：
56.9
通讯作者：
HALSTEAD, SB
中科院分区：
文献类型：
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作者：
HALSTEAD, SB
登革热病毒是由埃及伊蚊传播给人类的四种抗原性相关但不同的血清型。这些病毒通常在美洲和非洲热带地区引起良性综合征登革热，在东南亚儿童中引起严重综合征登革出血热/登革休克综合征(DHF/DSS)。这种严重的综合症最近在波多黎各感染该病毒的儿童中也被发现，其特点是血管通透性增加和异常止血。它发生在登革热免疫母亲所生的1岁以下婴儿和对一种血清型登革热病毒免疫并正在经历第二种血清型感染的1岁及以上儿童中。登革热病毒在单核巨噬细胞系的细胞中复制，亚中和浓度的登革热抗体增加了登革热病毒在这些细胞中的感染。这种抗体依赖的感染增强调节了人类的登革热疾病，尽管疾病的严重程度也可以通过基因控制，可能是通过允许和限制单核细胞中病毒的生长。单抗显示登革热病毒抗原表位的异质性分布。这些表位用于调节疾病：当针对共同抗原的抗体部分中和异型病毒时，感染和疾病就会受到抑制；仅增强抗体就会导致疾病反应增强。对登革热基因组结构的进一步了解应该会在理解登革热的致病机制方面取得快速进展。
Dengue viruses occur as four antigenically related but distinct serotypes transmitted to humans byAedes aegyptimosquitoes. These viruses generally cause a benign syndrome, dengue fever, in the American and African tropics, and a severe syndrome, dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS), in Southeast Asian children. This severe syndrome, which recently has also been identified in children infected with the virus in Puerto Rico, is characterized by increased vascular permeability and abnormal hemostasis. It occurs in infants less than 1 year of age born to dengue-immune mothers and in children 1 year and older who are immune to one serotype of dengue virus and are experiencing infection with a second serotype. Dengue viruses replicate in cells of mononuclear phagocyte lineage, and subneutralizing concentrations of dengue antibody enhance dengue virus infection in these cells. This antibody-dependent enhancement of infection regulates dengue disease in human beings, although disease severity may also be controlled genetically, possibly by permitting and restricting the growth of virus in monocytes. Monoclonal antibodies show heterogeneous distribution of antigenic epitopes on dengue viruses. These epitopes serve to regulate disease: when antibodies to shared antigens partially neutralize heterotypic virus, infection and disease are dampened; enhancing antibodies alone result in heightened disease response. Further knowledge of the structure of dengue genomes should permit rapid advances in understanding the pathogenetic mechanisms of dengue.