TY - JOUR
T1 - Dengue structure differs at the temperatures of its human and mosquito hosts
AU - Zhang, Xinzheng
AU - Sheng, Ju
AU - Plevka, Pavel
AU - Kuhn, Richard J.
AU - Diamond, Michael S.
AU - Rossmann, Michael G.
PY - 2013/4/23
Y1 - 2013/4/23
N2 - 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 ∼500 Å, and little exposed membrane at room temperature, the virions have a bumpy appearance with a diameter of ∼550 Å and some exposed membrane at 37 °C. The bumpy structure at 37 °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 °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.
AB - 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 ∼500 Å, and little exposed membrane at room temperature, the virions have a bumpy appearance with a diameter of ∼550 Å and some exposed membrane at 37 °C. The bumpy structure at 37 °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 °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.
KW - Cryo-EM
KW - Host temperature
KW - Irreversible and conformational change
KW - Temperature dependence
UR - http://www.scopus.com/inward/record.url?scp=84876842073&partnerID=8YFLogxK
U2 - 10.1073/pnas.1304300110
DO - 10.1073/pnas.1304300110
M3 - Article
C2 - 23569243
AN - SCOPUS:84876842073
SN - 0027-8424
VL - 110
SP - 6795
EP - 6799
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 17
ER -