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Antibody-dependent enhancement of heterotypic dengue infections involved in suppression of IFN? production

2001; Wiley; Volume: 63; Issue: 2 Linguagem: Inglês

10.1002/1096-9071(20000201)63

1096-9071

Kuender D. Yang, Wen‐Ting Yeh, Ming‐Yu Yang, Rong‐Fu Chen, Men‐Fang Shaio,

Vector-borne infectious diseases

Antibody-dependent enhancement has been implicated in some outbreaks of epidemic dengue hemorrhagic fever, however, the mechanism of antibody-dependent enhancement is not well known. This study was conducted to investigate the cross-protection and cross-enhancement of dengue-2 virus infections by dengue-1 immune sera. It was found that dengue-1 immune sera at 1:5 dilution (n = 12) could neutralize dengue-2 infections in BHK-21 cells, as assessed by a standard plaque-reduction neutralization assay. Two-thirds of the dengue-1 immune sera at 1:25 dilution demonstrated neutralizing effects for dengue-2 infections, whereas, non-immune sera revealed no neutralization for dengue-2 infections in BHK-21 cells. Human mononuclear leukocytes in response to dengue-2 infections elicited a T cell helper 1 (Th1) response revealing induction of IFNγ but not IL-4 production. Dengue-1 immune sera did not neutralize dengue-2 infections in mononuclear leukocytes. Subneutralizing titers of dengue-1 immune sera at 1:250, but not at 1:10 dilution, enhanced dengue-2 infections in mononuclear leukocytes (1.2 ± 0.7 × 104 vs. 2.8 ± 0.3 × 102 PFU/ml). The enhancement of dengue-2 infections in mononuclear leukocytes by dengue-1 immune sera at 1:250 was associated with an increase in the lymphocyte proliferation index, and a decrease in IFNγ production (56 ± 24 vs. 12 ± 3 pg/ml). The addition of IFNγ (0.1 μg/ml) suppressed significantly the antibody-dependent enhancement induced by dengue-1 immune sera, whereas the presence of anti-IFNγ F(ab)2 antibody augmented the antibody-dependent enhancement effect. Results from this study suggest that suppression of Th1 response may be involved in the antibody-dependent enhancement of heterotypic dengue infections. Better regulation of Th1/Th2 reactions may be useful for prevention of heterotypic immune enhancement of dengue infections. J. Med. Virol. 63:150–157, 2001. © 2001 Wiley-Liss, Inc.