The main objectives of this research are; 91) identify viral factors which may influence the severity of dengue infection in humans, by comparing specific viral genome differences with clinical and epidemiologic observations, and (20 to correlate these genome differences with human monocyte infection rates, a possible in vitro marker for human virulence. We will determine the present distribution of dengue virus genotypes, of serotype 2, in Bangkok, by phylogenetic analysis of 20 isolates, using limited sequencing techniques (comparison of 240 nucleotides from the E/NS1 gene junction). This study will provide preliminary data on disease associations with specific genotypes, as viruses are obtained from project 1. Experiments will be carried out to determine the feasibility of using the polymerase chain reaction (PCR) for the amplification of dengue virus RNA, for sequencing. We will determine if there is a correlation between disease severity and specific nucleotide differences in the virus genome, by comparing the complete genomic sequences of 6 dengue viruses of serotype 2 (3 pairs from matched D and DHF patients). These viruses will be selected from patients in one location, with complete clinical and immunologic workups (from projects 1 and 2), to assign them to each of two categories, D or DHF, and by whether the viruses replicate to high or low levels in human monocytes, a possible in vitro model of virulence. We will confirm and correlate significant genetic differences seen in the above mentioned viruses with those of 20 additional viruses from each of the two clinical categories (D and DHF), by sequencing the implicated areas of the genome. These molecular virology data will be combined with the detailed immunologic data (from Projects 1 and 2), to develop an improved model for interactions of human immune responses and dengue viral determinants that result in the production of severe dengue disease, and will provide data that will be useful in the development of dengue vaccine.
| Park, Sangshin; Srikiatkhachorn, Anon; Kalayanarooj, Siripen et al. (2018) Use of structural equation models to predict dengue illness phenotype. PLoS Negl Trop Dis 12:e0006799 |
| Salje, Henrik; Cummings, Derek A T; Rodriguez-Barraquer, Isabel et al. (2018) Reconstruction of antibody dynamics and infection histories to evaluate dengue risk. Nature 557:719-723 |
| Srikiatkhachorn, Anon; Mathew, Anuja; Rothman, Alan L (2017) Immune-mediated cytokine storm and its role in severe dengue. Semin Immunopathol 39:563-574 |
| Rattanamahaphoom, Jittraporn; Leaungwutiwong, Pornsawan; Limkittikul, Kriengsak et al. (2017) Activation of dengue virus-specific T cells modulates vascular endothelial growth factor receptor 2 expression. Asian Pac J Allergy Immunol 35:171-178 |
| Kalayanarooj, Siripen; Rothman, Alan L; Srikiatkhachorn, Anon (2017) Case Management of Dengue: Lessons Learned. J Infect Dis 215:S79-S88 |
| Kang, Jeon-Young; Aldstadt, Jared (2017) The Influence of Spatial Configuration of Residential Area and Vector Populations on Dengue Incidence Patterns in an Individual-Level Transmission Model. Int J Environ Res Public Health 14: |
| Moulton, Steven L; Mulligan, Jane; Srikiatkhachorn, Anon et al. (2016) State-of-the-art monitoring in treatment of dengue shock syndrome: a case series. J Med Case Rep 10:233 |
| Srikiatkhachorn, Anon; Yoon, In-Kyu (2016) Immune correlates for dengue vaccine development. Expert Rev Vaccines 15:455-65 |
| Rothman, Alan L; Ennis, Francis A (2016) Dengue Vaccine: The Need, the Challenges, and Progress. J Infect Dis 214:825-7 |
| Townsley, E; O'Connor, G; Cosgrove, C et al. (2016) Interaction of a dengue virus NS1-derived peptide with the inhibitory receptor KIR3DL1 on natural killer cells. Clin Exp Immunol 183:419-30 |
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