720A Mary Ellen Jones Bldg, CB #7290
Vector-borne disease pathogenesis
Blood feeding arthropods such as mosquitoes and ticks are responsible for the transmission of many infectious diseases to people and animals. Despite advances in many areas of public health, arthropod vector-borne diseases continue to be a significant problem, especially in poor, tropical countries. Moreover, in many parts of the world these diseases are increasing in frequency and expanding into new regions. Our group studies the tick-borne bacterium responsible for Lyme disease and the mosquito-borne Flavivirus responsible for Dengue.
Borrelia burgdorferi, the spirochete responsible for Lyme disease is transmitted by Ixodes ticks. Unlike most vector-borne diseases that dominate in the tropics, Lyme disease is mainly a problem in temperate countries in North America, Europe and Asia. Our studies on Lyme disease fall into four areas:
- Identification of bacterial genes required for tick stages of the life cycle and defining the specific function of these genes
- Defining the external signals and intracellular signaling pathways that regulate Borrelia gene expression in the tick
- Identification and characterization of tick proteins that facilitate infection and transmission
- Development of vaccines that block the transmission of spirochetes from feeding ticks.
Thus, the focus of our work is the vector stage of the Borrelia life cycle and we believe that these studies will expand our knowledge of vector-borne transmission in general.
Dengue is a mosquito-borne Flavivirus that is common in many tropical regions of the world. Some people, especially children, can develop a severe, life threatening, hemorrhagic disease following dengue infection. Human immunity to dengue is complex and under some conditions immunity can be protective, whereas under other conditions immunity can actually exacerbate disease. We are involved in a collaborative study with the Pediatric Dengue Vaccine Initiative to define the molecular basis of protective and non-protective human immune responses against dengue viruses. The long term goal of these studies is to help develop an effective and safe dengue vaccine. Dengue is an emerging disease in many parts of the world and we are currently studying the recent emergence of dengue hemorrhagic fever in Sri Lanka. This project involves laboratory studies with dengue strains linked to mild and severe disease outbreaks as well as epidemiological studies with samples and data collected in Sri Lanka. Our work on dengue in Sri Lanka is being conducted in collaboration with colleagues at the Genetech Research Institute in Colombo.
de Alwis R, Beltramello M, Messer WB, Sukupolvi-Petty S, Wahala WM, Kraus A, Olivarez NP, Pham Q, Brian J, Tsai WY, Wang WK, Halstead S, Kliks S, Diamond MS, Baric R, Lanzavecchia A, Sallusto F, de Silva AM (2011). Correction: in-depth analysis of the antibody response of individuals exposed to primary dengue virus infection. PLoS Negl Trop Dis. 5(8). doi: 10.1371/annotation/f585335f-ff77-40ae-a8b6-ad6019af31aa.
de Alwis R, Beltramello M, Messer WB, Sukupolvi-Petty S, Wahala WM, Kraus A, Olivarez NP, Pham Q, Brian J, Tsai WY, Wang WK, Halstead S, Kliks S, Diamond MS, Baric R, Lanzavecchia A, Sallusto F, de Silva AM (2011). In-depth analysis of the antibody response of individuals exposed to primary dengue virus infection. PLoS Negl Trop Dis. 5(6):e1188.
Wahala WM, Donaldson EF, de Alwis R, Accavitti-Loper MA, Baric RS, de Silva AM (2010). Natural strain variation and antibody neutralization of dengue serotype 3 viruses. PLoS Pathog. 6(3):e1000821.
Wahala WM, Kraus AA, Haymore LB, Accavitti-Loper MA, de Silva AM (2009). Dengue virus neutralization by human immune sera: role of envelope protein domain III-reactive antibody. Virology. 392(1):103-13.
Srivastava SY, de Silva AM (2009). Characterization of Borrelia burgdorferi aggregates. Vector Borne Zoonotic Dis. 9(3):323-9.
Hacker K, White L, de Silva AM (2009). N-linked glycans on dengue viruses grown in mammalian and insect cells. J Gen Virol. 90(Pt 9):2097-106.
de Silva AM, Tyson KR, Pal U (2009). Molecular characterization of the tick-Borrelia interface. Front Biosci. 14:3051-63. Review.
Srivastava SY, de Silva AM (2008). Reciprocal expression of ospA and ospC in single cells of Borrelia burgdorferi. J Bacteriol. 190(10):3429-33.
Tyson KR, Elkins C, de Silva AM (2008). A novel mechanism of complement inhibition unmasked by a tick salivary protein that binds to properdin. J Immunol. 180(6):3964-8.
Kraus AA, Messer W, Haymore LB, de Silva AM (2007). Comparison of plaque- and flow cytometry-based methods for measuring dengue virus neutralization.
J Clin Microbiol.45(11):3777-80.
Strother KO, Hodzic E, Barthold SW, de Silva AM (2007). Infection of mice with lyme disease spirochetes constitutively producing outer surface proteins a and B. Infect Immun. 75(6):2786-94.
Nosbisch LK, de Silva AM (2007). Lack of detectable variation at Borrelia burgdorferi vlsE locus in ticks. J Med Entomol. 44(1):168-70.
Strother, K.O., Broadwater, A. and A. M. de Silva. (2005). Plasmid requirements for infection of ticks by Borrelia burgdorferi. Vector-borne and Zoonotic Dis. 5(3): 237-245.
Strother, K.O. and de Silva AM (2005) Role of Borrelia burgdorferi linear plasmid 25 in infection of Ixodes scapularis ticks. Journal of Bacteriology. 187(16) 5776-81.
Lambeth, C.R., White, L.J., Johnston, R.E., and de Silva A.M. (2005). Flow cytometry based assay for titrating dengue virus. Journal of Clinical Microbiology. 43 (7) 3267-72.
Gipson, C.L. and de Silva A.M. (2005) Interactions of OspA Monoclonal Antibody C3.78 with Borrelia burgdorferi within Ticks. Infection and Immunity 73 (3) 1644-7.