Development of cross-reactive antibodies to plasminogen during the immune response to dengue virus infection.
The four serotypes of dengue virus (a mosquito-borne flavivirus) cause an acute febrile illness (dengue fever) or a more prolonged illness with plasma leakage resulting in hypovolemia (dengue hemorrhagic fever). Hemorrhage may accompany either. Epidemiologic data suggest a role for dengue antibodies in pathogenesis. Computer analysis revealed a 20-residue region of similarity in amino acid sequence between the dengue type 4 envelope glycoprotein (E) and a family of clotting factors, including plasminogen, the prime mediator of fibrinolysis. By use of synthetic peptides in ELISA, E antibodies that potentially bind plasminogen were detected in 75% of 40 Thai patients acutely infected with dengue virus type 1, 2, 3, or 4. Plasminogen cross-reactivity of dengue antibodies was shown to be specific for the related sites in E and plasminogen. The dengue E sequence with similarity to plasminogen is largely conserved within the currently known flavivirus E sequences. However, 15 Thai patients hospitalized for illness caused by Japanese encephalitis virus (a flavivirus not associated with hemorrhage) did not develop plasminogen-cross-reactive antibodies, and this finding correlated with failure of Japanese encephalitis virus antibodies to bind to the plasminogen-cross-reactive site in E.
Markoff
L J
LJ
Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892.
Innis
B L
BL
Houghten
R
R
Henchal
L S
LS
D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D000914:Antibodies, Viral / Q000096:biosynthesis*; D000956:Antigens, Viral / Q000737:chemistry; D001667:Binding, Competitive; D002648:Child; D002675:Child, Preschool; D003429:Cross Reactions; D003715:Dengue / Q000276:immunology*; D003716:Dengue Virus / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D007223:Infant; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D010958:Plasminogen / Q000737:chemistry / Q000276:immunology*; D012189:Retrospective Studies; D014759:Viral Envelope Proteins / Q000737:chemistry
D000914:Antibodies, Viral; D000956:Antigens, Viral; D014759:Viral Envelope Proteins; D010958:Plasminogen