Interactions between dengue type 3 viruses and human dendritic cells Public Deposited

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  • March 21, 2019
  • Lambeth, Cassandra Rashida
    • Affiliation: School of Medicine, Department of Microbiology and Immunology
  • Dengue is a mosquito-borne viral disease of global public health significance. Throughout the world more than 2.5 billion people are at risk of contracting dengue virus (DENV) infection. Each year, an estimated 100 million cases of dengue viral infection are reported worldwide with 250,000 people developing the more severe dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS), which is often fatal. The pathogenesis of dengue is poorly understood due to the lack of an animal model. Both host and viral factors are believed to play key roles in dengue pathogenesis and in clinical outcome. DENVs are difficult to study in culture because available assays are time consuming and typically used with high passage, laboratory adapted strains of the virus. I have developed flow cytometry-based assays to study DENVs. The assays were used to titer viruses and to measure virus-antibody interactions. The flow cytometry-based assays were also used to study interactions between DENVs and human dendritic cells (DCs), one of the primary targets of DENVs. Experiments were done to analyze interactions between Dengue type 3 viruses (DENV3) and primary human DCs. DENV3 blocked activation of infected immature DCs, but not the uninfected bystander DCs in the culture. Experiments were also conducted to characterize the ability of different strains of DENV3 to infect human DCs. I identified two Sri Lankan isolates of DENV3, one from a period of mild disease and the other from a period of severe disease, which infected DCs with different efficiency. Both viruses were equally sensitive to type I IFN, indicating that host anti-viral responses were unlikely to be responsible for observed differences. Both viruses also bound to cells with similar efficiency but entered cells at different rates. The two viruses differed at a step between binding to the cell surface and viral fusion in endosomes. The significance of these results with respect to the cell biology of DENVs and virus-host interactions are discussed.
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  • De Silva, Aravinda Manu
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