Washington: Researchers have thrown light on how immature dengue virus reproduces, which may pave the way to the development of anti-viral drugs against the disease.

A team including Purdue University's Michael Rossmann and Richard Kuhn has solved the structure of the immature dengue virus, which is related to West Nile virus and yellow fever. Dengue is a mosquito- borne pathogen that kills more than 24,000 people in the world annually.

The pair solved the structure of the mature dengue virus particle in 2002, and according to Rossmann, the new findings are a significant step toward unravelling the behaviour of viruses.

"We're beginning to dissect the individual steps in a virus' life cycle," said Rossmann, professor of Biological Sciences in Purdue's School of Science. "We hope to learn a great deal more about viral development so that approaches to preventing infection become conceivable."

The study, a collaboration among Rossmann, Kuhn and Tim Baker at Purdue and James Straus at the California Institute of Technology, appears in the June 2 issue of 'EMBO'.

The research group used an advanced imaging technique, known as cryoelectron microscopy, to take 3- D pictures of the dengue particle, the term experts use to denote a single virus. While viruses are not considered to be "alive" by the standards one applies to plants and animals, the team's images have revealed that particles go through a complex developmental process.

"We have discovered that an astonishing structural change occurs between the immature and mature dengue shells," said Kuhn, also professor of biology. "We don't yet know how it all happens – but even though we have only seen two points along the viral assembly line so far, we can tell it's quite a dynamic metamorphosis."

Compared to the mature dengue particle, for example, the immature form is 15 per cent greater in diameter.

"The immature particle is covered with 60 three-pronged protein spikes, called trimers, that jut from its surface," Kuhn said.

"In contrast, the mature particle is a nearly smooth sphere, like a golf ball. Somewhere in the assembly process, these trimers flatten out, making the surface appear more even."

The proteins are important because each contains a short amino acid sequence called a fusion peptide that the virus needs to attach itself to a potential host. Without this fusion peptide, the virus cannot successfully invade a cell.

It is in examining the changes a virus undergoes – for example, in the case of dengue, how it uncaps its fusion peptides to become an infectious agent – that the team hopes to find clues to stopping the developmental process in its tracks.

ANI