In Search of the Green Glow: Using Fluorescence to Detect Deadly Viruses

May 2012
Topics: Diseases, Disease Transmission
MITRE researchers are developing a new way of identifying deadly viruses.
petri dish in lab

In the 2011 film Contagion, Gwyneth Paltrow plays a business executive who collapses and dies only days after returning from an overseas trip. A short time later her son dies, and it's not long before similar cases spring up around the world. While the unknown contagion spreads, scientific researchers struggle to identify a vaccine as worldwide panic ensues.

Although a work of fiction, this Hollywood production depicts a grimly realistic scenario of a virus—a submicroscopic infectious agent that grows in living cells—and its potential consequences for global disaster. Widely acknowledged as a grave threat that could lead to a global pandemic, deadly viruses receive growing attention from the Centers for Disease Control and Prevention (CDC), National Institutes of Health, Department of Defense, the World Health Organization, and other international organizations. Not only a public health issue, viruses are also seen as a threat to national security.

In spite of the current best efforts of the public health community, a number of notorious viruses—influenza, HIV, and others—each year take an enormous toll on the world population. New and naturally occurring viruses, such as bird flu, pose additional threats. In addition, genetically modified viruses present yet another danger with potentially catastrophic implications.

A Spike in Fluorescent Activity

Since scientists identified the first virus in 1898, they have learned to recognize viruses based on a variety of criteria, including their surface characteristics, replication mechanisms, disease symptoms, and the affected species. Today, researchers primarily identify viruses either by using antibodies that bind to the surfaces of a virus or by a PCR (polymerase chain reaction)-based approach, which exploits the identification of specific DNA (deoxyribonucleic acid) or RNA (ribonucleic acid), two of the building blocks of living cells. The PCR-based approach requires exact knowledge of the virus' genetic make-up to identify it.

Recently a MITRE team has pursued virus identification from another angle: analysis of the spatial structure—the internal configuration—of a virus' genetic make-up. It's a new approach based on the replication mechanism within a family of viruses. "The concept of this novel technology is that since the replication mechanism is highly conserved within a family of viruses, we can use elements of that process to detect the presence of any member of the group," says Juan Arroyo, a principal molecular biology and immunology scientist, and the research team leader.

Currently the team is focusing its study on dengue fever virus, a virus subgroup that each year can affect up to 100 million people (see "Dengue Fever"). To help identify a virus, the team creates an artificial RNA model. Designed to mimic a virus' natural genetic configuration, the artificial RNA model provides a way for researchers to pinpoint the identity of a virus based on its reproductive process. When a virus reproduces and multiplies, its genetic material folds onto itself, creating unique signatures that act like a fingerprint. Although someone could potentially disguise or alter a virus, this genetic fingerprint within the folded genes will remain, because it's needed for viral replication. Therefore, this provides an important means of identification.

The Green Glow Is Key

Fluorescence plays a key role in the approach. The research team exploits the virus' natural reproductive process—the folding and unfolding of its genome—by adding fluorescent tags to these folds. To predict the folding, researchers depend on computational algorithms. When a virus infects the artificial RNA model, researchers can observe a spike in fluorescent activity.

"We're trying to tap into the idea that when a virus from a certain family infects your body, it's replicating in a recognizable fashion," says Arroyo. "Although new and unknown viruses contain unidentified genes and unfamiliar surface structures, they still maintain the reproduction machinery of a known precursor virus group. This allows them to multiply and cause disease."

Unraveling Genome Spatial Configurations

This new technology has won the attention of the healthcare community. Arroyo and his team are currently working with the National Cancer Institute to further unravel genome spatial configurations to help identify viruses of the Flavivirus group, which includes dengue fever and other viruses, such as West Nile.

Other organizations have also expressed interest. "We have entered into collaboration with Oak Ridge National Laboratory to explore methods to monitor infection by using implantable biosensors to deliver fluorescent tags to tissue lesions caused by viral infection," Arroyo says.

"We're also collaborating with the Army to develop tags for another family of interest to the U.S. Army Medical Research Institute of Infectious Diseases researchers. With the knowledge gained working with dengue virus, we can predict the folding requirements and build tags for other groups of viruses."

MITRE has also entered into an agreement with the CDC. According to Arroyo, in the first quarter of 2012, MITRE will provide the CDC with a transgenic cell line that delivers a fluorescent tag. "The CDC wants to test our cell lines for future incorporation into their first-tier detection protocols for dengue viruses and other pathogenic members of the group."

Developing this technology will also allow detection of unknown or modified viruses. The methods offer a promising capability that can help ensure national security and public health. Arroyo feels confident about his team's work and its potential to contribute to bio-sensing technology. "You can disguise or alter a virus, but you cannot change the way the virus replicates."

—by Elvira Caruso


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