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

TALARICO, LAURA B.; BATALLE, JUAN P.; BYRNE, ALANA B.; BRAHAMIAN, JORGE M.; FERRETTI, ADRIÁN; GARCÍA, AYELÉN G.; MAURI, ALDANA; SIMONETTO, CARLA; HIJANO, DIEGO R.; LAWRENCE, ANDREA; ACOSTA, PATRICIO L.; CABALLERO, MAURICIO T.; ROJAS, YÉSICA PAREDES; IBAÑEZ, LORENA I.; MELENDI, GUILLERMINA A.; REY, FÉLIX A.; DAMONTE, ELSA B.; HARRIS, EVA; POLACK, FERNANDO P.

EBioMedicine

Cell Press / Elsevier

Año: 2017

2352-3964

Dengue is the mostprevalent arthropod-borne viral disease worldwide and is caused by the fourdengue virus serotypes (DENV-1-4). Sequential heterologous DENV infections canbe associated with severe disease manifestations. Here, we present animmunocompetent mouse model of secondary DENV infection using non mouse-adaptedDENV strains to investigate the pathogenesis of severe dengue disease. C57BL/6mice infected sequentially with DENV-1 (strain Puerto Rico/94) and DENV-2(strain Tonga/74) developed low platelet counts, internal hemorrhages, andincrease of liver enzymes. Cross-reactive CD8+ T lymphocytes were found to benecessary and sufficient for signs of severe disease by adoptively transferringof DENV-1-immune CD8+T lymphocytes before DENV-2 challenge. Disease signs wereassociated with production of tumor necrosis factor (TNF)-α and elevatedcytotoxicity displayed by heterotypic anti-DENV-1 CD8+ T lymphocytes. Thesefindings highlight the critical role of heterotypic anti-DENV CD8+ Tlymphocytes in manifestations of severe dengue disease.