Environmental influences on antibody-enhanced dengue disease outcomes

Diniz, Daniel Guerreiro, Fôro, César Augusto Raiol, Turiel, Maíra C.Pereira, Sosthenes, Marcia C.K., Demachki, Sâmia, Gomes, Giovanni Freitas, Rego, Carla M.Damasceno, Magalhães, Marina Cutrim, Pinho, Brunno Gomes, Ramos, Juliana Pastana, Casseb, Samir M.Moraes, Brito, Maysa de Vasconcelos, da Silva, Eliana Vieira Pinto, Nunes, Marcio Roberto Teixeira, Diniz, José Antonio Picanço, Cunningham, Colm, Perry, Victor Hugh, Vasconcelos, Pedro F.Costa and Diniz, Cristovam W.Picanço (2012) Environmental influences on antibody-enhanced dengue disease outcomes. Memorias do Instituto Oswaldo Cruz, 107 (8), 1021-1029. (doi:10.1590/S0074-02762012000800010).

Abstract

Because an enriched environment (EE) enhances T-cell activity and T-lymphocytes contribute to immunopatho- genesis during heterologous dengue virus (DENV) infections, we hypothesised that an EE increases dengue severity. To compare single serotype (SS) and antibody-enhanced disease (AED) infections regimens, serial intraperitoneal were performed with DENV3 (genotype III) infected brain homogenate or anti-DENV2 hyperimmune serum followed 24 h later by DENV3 (genotype III) infected brain homogenate. Compared AED for which significant differences were detected between the EE and impoverished environmental (IE) groups (Kaplan-Meyer log-rank test, p = 0.0025), no significant differences were detected between the SS experimental groups (Kaplan-Meyer log-rank test, p = 0.089). Survival curves from EE and IE animals infected with the AED regimen were extended after corticoid injection and this effect was greater in the EE than in the IE group (Kaplan-Meyer log-rank test, p = 0.0162). Under the AED regimen the EE group showed more intense clinical signs than the IE group. Dyspnoea, tremor, hunched posture, ruffled fur, immobility, pre-terminal paralysis, shock and death were associated with dominant T-lympho- cytic hyperplasia and presence of viral antigens in the liver and lungs. We propose that the increased expansion of these memory T-cells and serotype cross-reactive antibodies facilitates the infection of these cells by DENV and that these events correlate with disease severity in an EE.

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