UF researchers uncover new keys to understanding WNV infection

GAINESVILLE, FLA. — A new gene microarray containing hundreds of pieces of DNA strands could be the key to understanding the brain responses of horses infected with West Nile virus (WNV), according to a new study from the University of Florida (UF) College of Veterinary Medicine.

Researchers believe the microarray, or "gene chip," could lead to better way to diagnose and treat horses and humans suffering from WNV.

Help on the horizon: A "gene chip" that targets genes active during brain disease states in horses may lead to new diagnostic tests and treatments for horses infected with West Nile virus.

"We hope this will help us understand why some animals and humans become sick and others succumb to the virus resulting in severe illness, lifelong neurological debilitation and even death," says senior author Maureen Long, DVM, PhD, Dipl. ACVIM, an associate professor of infectious diseases and pathology at the UF veterinary college. "Knowing this will allow us to come up with treatments that aid in recovery from illness."

Long's former graduate student and lead author of the study, Melissa Bourgeois, created a gene library enriched for neurological and immunological sequences to develop the novel chip, which will help target genes that are active during brain disease states.

When the DNA strands, also called probes, in the "gene chip" are exposed to genetic material from equine cells, researchers can identify which genes are associated with equine brain disease. Agilent Technologies of California patented the probes on behalf of UF, according to the university.

The study ultimately revealed that the equine brain chip consists of 41,040 genes. For West Nile virus, Long and Bourgeois determined that certain families of genes change in a consistent manner during infection, during the disease and recovery from the WNV-associated encephalitis.

"Although we knew there were microarrays that had previously been developed for horses, our goal was to create a brain and inflammation-based array to look specifically at how function was affected during brain infection," says Long, who is also a member of the UF Emerging Pathogens Institute. "This chip has applications to many brain and spinal abnormalities of the horse including eastern equine encephalitis, equine protozoal myelitis, rabies and even non-infectious diseases like Wobbler syndrome. This allowed us to detect changes that would not be common in normal horses."

Since 1999, more than 24,000 cases of West Nile virus encephalitis have been reported in horses in the United States. In 2006, there was a 14 percent increase in human cases and new expansion of the virus into 52 U.S. counties, according to UF.

Bourgeois, who now works in the influenza division at the Centers for Disease Control and Prevention, says the information uncovered by the research she did at UF could lead to new tools to combat WNV, as well as a model to understand and reduce the impact of viral encephalitis.

The UF study took more than five years and relied on sequencing and bioinformatics expertise provided by UF's Interdisciplinary Centers for Biotechnology Research. The research was published in the October issue of PloS One. Collaborators include UF's Nancy Denslow, a professor of physiological sciences; David Barber, formerly an assistant professor of physiological sciences at UF; and Kathy Seino, an assistant professor at Washington State University.