Stopping Dengue in its tracks

2010

Challenge

Dengue virus is estimated to cause close to 400 million infections and half a million hospitalizations annually, the majority of which involve children . Due to the lack of effective therapies and vaccines and the increasing geographic range of the mosquitoes carrying the virus, this infectious tropical disease is a growing threat to global health and economies.

Advance

IRP researchers led by Leonid Chernomordik, Ph.D., focused on understanding how the dengue virus fuses with various organelles to deliver its RNA into human cells. The team discovered a series of cellular cofactors essential for the fusion process and successful dengue virus infection.

Impact

The finding explains a specific intracellular localization of dengue fusion and led to the development of broadly neutralizing antibodies that inhibit the early fusion stages of dengue virus infection. In addition, the team’s research yielded the first quantitative assays for screening these antiviral therapies, uncovering a new path towards the development of a vaccine against dengue virus.

Publications

Zaitseva E, Yang ST, Melikov K, Pourmal S, Chernomordik LV. (2010). Dengue virus ensures its fusion in late endosomes using compartment-specific lipids. PLoS Pathog. 6(10), e1001131. doi: 10.1371/journal.ppat.1001131.

Costin JM, Zaitseva E, Kahle KM, Nicholson CO, Rowe DK, Graham AS, Bazzone LE, Hogancamp G, Figueroa Sierra M, Fong RH, Yang ST, Lin L, Robinson JE, Doranz BJ, Chernomordik LV, Michael SF, Schieffelin JS, Isern S. (2013). Mechanistic study of broadly neutralizing human monoclonal antibodies against dengue virus that target the fusion loop. J Virol. 87(1), 52-66.