Researchers have discovered that rising temperature induces key changes in the dengue virus when it enters its human host, and the findings represent a new approach for designing vaccines against the aggressive mosquito-borne pathogen.
The researchers found that the dengue virus particles swell slightly and take on a bumpy appearance when heated to human body temperature, exposing "epitopes," or regions where antibodies could attach to neutralize the virus.
The discovery is significant because it could help to explain why vaccines against dengue have been ineffective, said Michael G. Rossmann, Hanley Distinguished Professor of Biological Sciences at Purdue University.
Scientists have been designing vaccines targeting the virus's smooth appearance found at the cooler temperatures of mosquitoes and ticks.
"The bumpy form of the virus would be the form present in humans, so the optimal dengue virus vaccines should induce antibodies that preferentially recognize epitopes exposed in that form," Rossmann said.
The findings are detailed in a research paper appearing online last week in Proceedings of the National Academy of Sciences.
The researchers used a technique called cryo-electron microscopy to see the three-dimensional structure of the virus at temperatures ranging from 28-37 degrees Celsius (37 degrees Celsius is 98.6 degrees Fahrenheit, or human body temperature). Findings showed that the virus has a smooth appearance while at the cooler temperatures found in mosquito or tick vectors, but then it morphs into the bumpy form at warmer temperatures before fusing to the host cell and delivering its genetic material.
"These findings were a big surprise," said Richard J. Kuhn, professor and head of Purdue's Department of Biological Sciences and director of the Bindley Bioscience Center. "No one expected to see the virus change its appearance as it moves from the mosquito to humans."