Turning up the heat on dengue
medwireNews: Research published in the Proceedings of the National Academy of Sciences shows that dengue virus particles or virions change their shape at human body temperature.
The team, led by Michael Rossman (Purdue University, West Lafayette, Indiana, USA), says that this may help explain why previous attempts to design a vaccine for the dengue virus have been unsuccessful to date.
Previous vaccines designed to combat the virus have been modeled on the smooth surface and smaller diameter (around 500 Å) of the virion particles seen at room temperature and in the mosquito and tick vectors. However, the work of Rossman and colleagues shows that at 37°C the virions have a bumpy surface and an expanded diameter (around 550 Å).
"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," explained Rossmann in a press statement.
The researchers used cryo-electron microscopy to visualize the three-dimensional structure of the dengue virions at temperatures ranging from 28 to 37°C. They found that the particles gradually morph from their original smooth surfaced structure to the bumpy form (at about 33°C) before fusing to the host cell prior to delivering its genetic information.
"These findings were a big surprise," co-author Richard Kuhn, also from Purdue University, told the press. "No one expected to see the virus change its appearance as it moves from the mosquito to humans."
Regarding vaccine design, "the change in dengue virus structure at temperatures above 33 °C should be considered," say the researchers, "given the poor correlation between neutralizing antibody titers and protection that was observed in the recent phase 2b DENV vaccine trial."
As dengue is a flavivirus, the findings could also apply to related diseases such as West Nile virus, suggest the authors, although they concede that further research is needed to investigate this possibility.
medwireNews (www.medwirenews.com) is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2013
By Helen Albert, Senior medwireNews Reporter