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Publication : The Role of Heterotypic DENV-specific CD8<sup>+</sup>T Lymphocytes in an Immunocompetent Mouse Model of Secondary Dengue Virus Infection.

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.
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