title: Environmental influences on antibody-enhanced dengue disease outcomes.
abstract: 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.
authors.affiliation: Laboratório de Investigações em Neurodegeneração e Infecção, Hospital Universitário João de Barros Barreto, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brasil.
authors.forename: Daniel Guerreiro
authors.initials: DG
authors.lastname: Diniz
authors.forename: César Augusto Raiol
authors.initials: CA
authors.lastname: Fôro
authors.forename: Maíra C Pereira
authors.initials: MC
authors.lastname: Turiel
authors.forename: Marcia C K
authors.initials: MC
authors.lastname: Sosthenes
authors.forename: Sâmia
authors.initials: S
authors.lastname: Demachki
authors.forename: Giovanni Freitas
authors.initials: GF
authors.lastname: Gomes
authors.forename: Carla M Damasceno
authors.initials: CM
authors.lastname: Rego
authors.forename: Marina Cutrim
authors.initials: MC
authors.lastname: Magalhães
authors.forename: Brunno Gomes
authors.initials: BG
authors.lastname: Pinho
authors.forename: Juliana Pastana
authors.initials: JP
authors.lastname: Ramos
authors.forename: Samir M Moraes
authors.initials: SM
authors.lastname: Casseb
authors.forename: Maysa de Vasconcelos
authors.initials: Mde V
authors.lastname: Brito
authors.forename: Eliana Vieira Pinto
authors.initials: EV
authors.lastname: da Silva
authors.forename: Marcio Roberto Teixeira
authors.initials: MR
authors.lastname: Nunes
authors.forename: José Antonio Picanço
authors.initials: JA
authors.lastname: Diniz
authors.forename: Colm
authors.initials: C
authors.lastname: Cunningham
authors.forename: Victor Hugh
authors.initials: VH
authors.lastname: Perry
authors.forename: Pedro F Costa
authors.initials: PF
authors.lastname: Vasconcelos
authors.forename: Cristovam W Picanço
authors.initials: CW
authors.lastname: Diniz
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D019067:Antibody-Dependent Enhancement / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D003715:Dengue / Q000276:immunology* / Q000821:virology; D003716:Dengue Virus / Q000276:immunology*; D004463:Ecology; D005260:Female; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000914:Antibodies, Viral