Pathogenesis of dengue: challenges to molecular biology.
Dengue viruses occur as four antigenically related but distinct serotypes transmitted to humans by Aedes aegypti mosquitoes. 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.
Halstead
S B
SB
Division of Health Sciences, Rockefeller Foundation, New York, NY 10036.
D000293:Adolescent; D000914:Antibodies, Viral / Q000502:physiology; D000956:Antigens, Viral / Q000276:immunology; D001210:Asia, Southeastern; D002648:Child; D002675:Child, Preschool; D003462:Cuba; D003715:Dengue / Q000453:epidemiology / Q000208:ethnology / Q000209:etiology* / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control; D003716:Dengue Virus / Q000145:classification / Q000235:genetics / Q000276:immunology / Q000502:physiology; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D011647:Puerto Rico; D012703:Serotyping
D000914:Antibodies, Viral; D000956:Antigens, Viral