Cryo-Electron Microscope Study Follows Changes in Dengue Fever Virus Morphology

The disease, which has no specific treatment, occurs in both epidemic and sporadic form in warm climates. The classic symptoms, following an incubation period of five to eight days, are high fever, chills, severe headache, pain in the joints, pain behind the eyes, rash, sweating, and prostration, but infected persons may experience milder symptoms. Symptoms subside in two to four days, but after a remission lasting from a few hours to two days there is another rise in temperature, and a generalized rash appears. Dengue hemorrhagic fever, a severe form of the disease, can cause hemorrhage, shock, and encephalitis. It occurs when a person who has acquired immunity to one of the viruses that cause dengue fever is infected by a different dengue virus; antibodies to the first dengue infection apparently work to aid the second virus. It is a leading cause of death among children in Southeast Asia and in recent years has become increasingly prevalent in tropical America.

Investigators at Purdue University (West Lafayette, IN, USA) used a cryo-electron microscope to examine changes in morphology of the dengue virus as it warmed from 28 °C (the temperature found in mosquito or tick vectors) to the human body temperature of 37 °C. Cryo-electron microscopy allows the observation of specimens that have not been stained or fixed in any way, showing them in their native environment while integrating multiple images to form a three-dimensional model of the sample.

The investigators reported in the April 8, 2013, online edition of the journal Proceedings of the National Academy of Sciences of the United States of America (PNAS) that at room temperature the virus had a smooth surface with a diameter of about 50 nanometers and little exposed membrane, while at human body temperature the virions had a bumpy appearance with a diameter of nearly 55 nanometers and some exposed membrane. The bumpy structure at 37 °C was similar to the previously predicted structure of an intermediate between the smooth form seen at lower temperatures and the mature form of the virus seen at the time of host cell invasion.

"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," said senior author Dr. Michael G. Rossmann, professor of biological sciences at Purdue University.

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