Findings reveal how dengue virus matures, becomes infectious

This composite shows an image of the dengue virus, top left, taken with cryoelectron microscopy, and, to the right of that image are reconstructions of how virus particles mature as... Click here for more information.

WEST LAFAYETTE, Ind. - Biologists at Purdue University have determined why dengue virus particles undergo structural changes as they mature in host cells and how the changes are critical for enabling the virus to infect new host cells.

The findings pertain to all viruses in the family of flaviviruses, which includes a number of dangerous insect-borne diseases such as dengue, West Nile, yellow fever and St. Louis encephalitis. Dengue is prevalent in Southeast Asia, Central America and South America. The virus, which is spread by mosquitoes, infects more than 50 million people annually, killing about 24,000 each year, primarily in tropical regions.

The researchers detailed critical changes that take place as the virus is assembled and moves from the inner to the outer portions of its host cell before being secreted so that it can infect other cells. Virus particles are exposed to progressively less acidic conditions as they traverse this "secretory pathway," and this changing acidity plays a vital role in the maturation of the virus.

"This is possibly the most detailed understanding of how any virus matures," said Michael Rossmann, the Hanley Distinguished Professor of Biological Sciences.

The research is a collaboration of work in two laboratories at Purdue, one operated by Rossmann and other operated by Jue Chen, an associate professor of biological sciences. They led the research with I-Mei Yu, a postdoctoral research associate working with Chen; and Long Li, a doctoral student working with Rossmann.

Findings are detailed in two back-to-back research papers appearing Friday (March 28) in the journal Science. The papers' co-authors include Yu, Li, Rossmann, Chen and Richard J. Kuhn, a professor and head of Purdue's Department of Biological Sciences.

Whereas the pathway for viruses entering new host cells has been studied extensively, the route for viruses moving out of their original host cells is not well-understood, Rossmann said.

"These two papers concern that route and compare the differences between both pathways," he said.

The virus moves through compartments inside the cell called the endoplasmic reticulum and the trans-Golgi network. While immature, virus particles are incapable of fusing with cell membranes, preventing them from infecting their own host cells and ensuring their maturation. Once mature, however, the virus is able to fuse to cell membranes, a trait that enables virus particles to infect new host cells, Chen said.