Dengue (DENV) has re-emerged in the last 25 years as one of the most significant emerging infectious diseases worldwide, posing a significant category A biodefense threat to the United States with ongoing epidemics in Puerto Rico, and recent outbreaks in Hawaii (2001) and Texas (1999, 2005, 2006). Its global resurgence, while partly explained by changing human demographics, increasing hyperendemicity, and mosquito vector expansions, remains poorly understood, especially with respect to the importance of virus evolution. We fill this critical gap by conducting a comparative evolutionary examination of DENV strains undergoing epidemic expansion, from replicate populations across the Asia-Pacific arena, paired with directed tissue and animal model assays for changes in virus phenotype related to epidemics. Our long-term goal is to resolve how viral genetic change drives disease emergence. The objective of the proposed research is to characterize evolution in dengue viruses isolated from epidemics relative to their endemic forms and confirm the impact of genetic changes in experimental models, the rationale being that identification of such viral genetic changes and their mechanisms of fixation will illuminate determinants of dengue epidemic potential and ultimately pathogenesis.
Specific Aim 1 : Determine the evolution of DENV between endemic and epidemic transmission phases to identify synapomorphies of higher epidemic potential.
Specific Aim 2 : Confirm the relationship between genetic changes in DENV epidemic strains and their phenotypic effects in in vitro models.
Specific Aim 3 : Confirm the relationship between genetic changes in DENV epidemic strains and their phenotypic effects in in vivo models
This research is highly relevant in that by clarifying the evolutionary mechanisms behind increasing epidemic severity in DENV, it elucidates evolution's role in disease emergence in general, especially important given the many vector-borne and zoonotic infectious diseases recently threatening the US (e.g., SARS, West Nile Virus, Avian Influenza, and HIV).
|Tsai, Wen-Yang; Youn, Han Ha; Tyson, Jasmine et al. (2018) Use of Urea Wash ELISA to Distinguish Zika and Dengue Virus Infections. Emerg Infect Dis 24:1355-1359|
|Thongsripong, Panpim; Chandler, James Angus; Green, Amy B et al. (2018) Mosquito vector-associated microbiota: Metabarcoding bacteria and eukaryotic symbionts across habitat types in Thailand endemic for dengue and other arthropod-borne diseases. Ecol Evol 8:1352-1368|
|Katzelnick, Leah C; Ben-Shachar, Rotem; Mercado, Juan Carlos et al. (2018) Dynamics and determinants of the force of infection of dengue virus from 1994 to 2015 in Managua, Nicaragua. Proc Natl Acad Sci U S A 115:10762-10767|
|Clemens, Daniel L; Lee, Bai-Yu; Horwitz, Marcus A (2018) The Francisella Type VI Secretion System. Front Cell Infect Microbiol 8:121|
|Barbour, Alan G (2017) Infection resistance and tolerance in Peromyscus spp., natural reservoirs of microbes that are virulent for humans. Semin Cell Dev Biol 61:115-122|
|Huwyler, Camille; Heiniger, Nadja; Chomel, Bruno B et al. (2017) Dynamics of Co-Infection with Bartonella henselae Genotypes I and II in Naturally Infected Cats: Implications for Feline Vaccine Development. Microb Ecol 74:474-484|
|Norris, Michael H; Heacock-Kang, Yun; Zarzycki-Siek, Jan et al. (2017) Burkholderia pseudomallei natural competency and DNA catabolism: Identification and characterization of relevant genes from a constructed fosmid library. PLoS One 12:e0189018|
|Marques, Adriana R; Yang, Xiuli; Smith, Alexis A et al. (2017) Citrate Anticoagulant Improves the Sensitivity of Borreliella (Borrelia) burgdorferi Plasma Culture. J Clin Microbiol 55:3297-3299|
|Nualnoi, Teerapat; Norris, Michael H; Tuanyok, Apichai et al. (2017) Development of Immunoassays for Burkholderia pseudomallei Typical and Atypical Lipopolysaccharide Strain Typing. Am J Trop Med Hyg 96:358-367|
|Parameswaran, Poornima; Wang, Chunling; Trivedi, Surbhi Bharat et al. (2017) Intrahost Selection Pressures Drive Rapid Dengue Virus Microevolution in Acute Human Infections. Cell Host Microbe 22:400-410.e5|
Showing the most recent 10 out of 467 publications