AI Article Synopsis
- Dengue is the world's most common viral disease transmitted by insects, caused by four different dengue virus types (DENV-1 to DENV-4), and can lead to severe illness after sequential infections.
- Researchers developed a mouse model to study severe dengue disease using strains that are not adapted for mice, showing that prior infection with DENV-1 followed by DENV-2 leads to serious health issues like low platelet counts and internal bleeding.
- The study found that cross-reactive CD8 T lymphocytes from DENV-1 infections play a crucial role in causing severe symptoms during secondary infections, linked to increased levels of a cytokine called tumor necrosis factor (TNF)-α.
Article Abstract
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 CD8T 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5478214 | PMC |
| http://dx.doi.org/10.1016/j.ebiom.2017.04.033 | DOI Listing |
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