First Author | Talarico LB | Year | 2017 |
Journal | EBioMedicine | Volume | 20 |
Pages | 202-216 | PubMed ID | 28483582 |
Mgi Jnum | J:269400 | Mgi Id | MGI:6268972 |
Doi | 10.1016/j.ebiom.2017.04.033 | Citation | Talarico LB, et al. (2017) The Role of Heterotypic DENV-specific CD8(+)T Lymphocytes in an Immunocompetent Mouse Model of Secondary Dengue Virus Infection. EBioMedicine 20:202-216 |
abstractText | 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)-alpha 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. |