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© Research
Publication : EBioMedicine

The Role of Heterotypic DENV-specific CD8+T Lymphocytes in an Immunocompetent Mouse Model of Secondary Dengue Virus Infection.

Team: UMR3569 – Virology
Team: Structural Virology
Member: Félix A. Rey
Scientific Fields
Diseases
Organisms
Applications
Technique

Published in EBioMedicine - 01 Jun 2017

Talarico LB, Batalle JP, Byrne AB, Brahamian JM, Ferretti A, García AG, Mauri A, Simonetto C, Hijano DR, Lawrence A, Acosta PL, Caballero MT, Paredes Rojas Y, Ibañez LI, Melendi GA, Rey FA, Damonte EB, Harris E, Polack FP

Link to Pubmed [PMID] – 28483582

Link to DOI – 10.1016/j.ebiom.2017.04.033

EBioMedicine 2017 Jun; 20(): 202-216

Dengue is the most prevalent arthropod-borne viral disease worldwide and is caused by the four dengue virus serotypes (DENV-1-4). Sequential heterologous DENV infections can be associated with severe disease manifestations. Here, we present an immunocompetent mouse model of secondary DENV infection using non mouse-adapted DENV strains to investigate the pathogenesis of severe dengue disease. C57BL/6 mice infected sequentially with DENV-1 (strain Puerto Rico/94) and DENV-2 (strain Tonga/74) developed low platelet counts, internal hemorrhages, and increase of liver enzymes. Cross-reactive CD8+ T lymphocytes were found to be necessary and sufficient for signs of severe disease by adoptively transferring of DENV-1-immune CD8+T lymphocytes before DENV-2 challenge. Disease signs were associated with production of tumor necrosis factor (TNF)-α and elevated cytotoxicity displayed by heterotypic anti-DENV-1 CD8+ T lymphocytes. These findings highlight the critical role of heterotypic anti-DENV CD8+ T lymphocytes in manifestations of severe dengue disease.