Study provides insight into Dengue virus reproduction

Duke University researchers recently conducted a study that showed how the Dengue virus reproduces in an infected individual without triggering the body’s normal defense mechanisms.

According to the study, the virus slowly takes over the endoplasmic reticulum, an accordion-shaped structure in the cell that serves as the site for the production of a small subset of host proteins. It stays away from cytosol, the large fluid-filled part of the cell where most cellular proteins are made.

This is in contrast to how most other viruses behave, aggressively disrupting the functions of the host to support their own needs. The dengue virus’ more subtle tactic allows it to avoid setting off the body’s normal defenses.

“It is a remarkably clever thing for a mere 10 kilobases of genetic information,” Christopher V. Nicchitta, the senior study author and professor of cell biology at Duke University School of Medicine, said. “The virus takes over the machinery and makes a ton of itself, but so slowly and inefficiently that it doesn’t set off any of the sensors the host cell uses to detect when something is awry.”

According to the World Health Organization, approximately 96 million people are sickened by dengue each year, but no treatment specific to dengue fever currently exists. Decades of vaccine research have been unsuccessful. Recent reports even suggest that a new vaccine for dengue might worsen the disease rather than prevent it.

“If you can’t make a vaccine, the approach you are left with involves understanding the precise molecular details of the life cycle of these viruses and how they are able to secure and manipulate the host machinery, so you can identify potential drug targets,” Nicchitta said. “It is a more difficult path, but we are beginning to map it out.”

The study was published on Jan. 10 in the Journal of Virology.

Nicchitta is currently working to identify which features of dengue cause its slow and steady behavior. He said that, although it sounds counterintuitive, if the virus were translated more efficiently, it could no longer go undetected, enabling the host cell to get rid of it.