4.8 Article

Dengue structure differs at the temperatures of its human and mosquito hosts

Publisher

NATL ACAD SCIENCES
DOI: 10.1073/pnas.1304300110

Keywords

host temperature; irreversible and conformational change; temperature dependence; cryo-EM

Funding

  1. National Institutes of Health [R01 AI76331, R01-AI077955]
  2. Purdue University

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We report on a conformational transition of dengue virus when changing the temperature from that present in its mosquito vectors to that of its human host. Using cryoelectron microscopy, we show that although the virus has a smooth surface, a diameter of similar to 500 angstrom, and little exposed membrane at room temperature, the virions have a bumpy appearance with a diameter of similar to 550 angstrom and some exposed membrane at 37 degrees C. The bumpy structure at 37 degrees C was found to be similar to the previously predicted structure of an intermediate between the smooth mature and fusogenic forms. As humans have a body temperature of 37 degrees C, the bumpy form of the virus would be the form present in humans. Thus, optimal dengue virus vaccines should induce antibodies that preferentially recognize epitopes exposed on the bumpy form of the virus.

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