Environmental influences on antibody-enhanced dengue disease outcomes

• Main Authors: Daniel Guerreiro Diniz, César Augusto Raiol Fôro, Maíra C Pereira Turiel, Marcia CK Sosthenes, Sâmia Demachki, Giovanni Freitas Gomes, Carla M Damasceno Rego, Marina Cutrim Magalhães, Brunno Gomes Pinho, Juliana Pastana Ramos, Samir M Moraes Casseb, Maysa de Vasconcelos Brito, Eliana Vieira Pinto da Silva, Marcio Roberto Teixeira Nunes, José Antonio Picanço Diniz, Colm Cunningham, Victor Hugh Perry, Pedro F Costa Vasconcelos, Cristovam W Picanço Diniz
• Format: Article
• Language: English
• Published: Instituto Oswaldo Cruz, Ministério da Saúde 2012-12-01
• Series: Memórias do Instituto Oswaldo Cruz.
• Subjects: experimental dengue infection; enriched environment; antibody-enhanced dengue disease; serial dengue infection; T-lymphocytes
• Online Access: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762012000800010&lng=en&tlng=en

Because an enriched environment (EE) enhances T-cell activity and T-lymphocytes contribute to immunopathogenesis 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-lymphocytic 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.