UCR-led study identifies crucial mechanism involved in immune response against viruses

Study on fruit flies offers new approach to understand human response to viral infections

A research team led by UC Riverside scientists has shown that the common fruit fly can serve as an excellent model for studying the immunity animals are born with for fighting viral infections. The research will help scientists better understand how our own bodies respond to viral infections, enabling more effective drugs to combat them.

Much is known among scientists about the fruit fly's innate immunity the immunity it is born with against bacterial and fungal pathogens, but little is known about the insect's antiviral response. The new research provides the first evidence that "RNA silencing" acts as an innate immunity mechanism to protect fruit flies from infection by viruses.

RNA, which is short for ribonucleic acid, is a molecule present in the cells of all living beings and required to synthesize proteins. RNA silencing refers to the specific destruction of RNA to inhibit the expression of a gene. Also called RNA interference (RNAi), the mechanism controls expression of more than one third of human genes.

Study results appear in the March 23 issue of Science Express.

"We've been able to pinpoint which mechanism protects fruit flies against viral infections," said Shou-Wei Ding, a professor of plant pathology at UCR and the lead author of the paper. "We now understand how this viral immunity works at the molecular level. Our work shows that it is the genes involved in RNA silencing that play a crucial role in the ability of fruit flies to overcome viral infection."

Viruses are tiny pockets of proteins packaging either DNA or RNA as the genetic material. They reproduce only inside a host's living cell, unlike bacterial and fungal pathogens, and are responsible for some of the most serious communicable diseases, such as influenza, herpes, hepatitis B and C, and HIV.

"There has been no consensus among scientists on how the fruit fly responds to viral infection," Ding said. "Our paper shows that upon viral infection fruit flies mount an RNAi-mediated antiviral response that specifically destroys the virus RNA but not the host RNA, thereby protecting flies against viral infection. Without an active RNAi pathway, flies would die quickly. This pathway is known to be common between fruit flies and humans, and likely to be protecting us, too, against viral infection."

In their paper, the researchers identify the major players in the viral immunity. These include the viral molecule that triggers the fly's immune response and the fruit fly genes that recognize and destroy the virus.

The fruit fly is a powerful tool and a classic laboratory model for understanding human diseases and genetics because it shares many genes and biochemical pathways with humans. More than 60 percent of disease genes found in humans are similar to genes in the fruit fly.

Ding's research group will begin working next on understanding the genetic component of the flies' immunity and how it is regulated. Ding's lab also will investigate how pathogens counteract the host's immunity.

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Xiao-Hong Wang, Roghiyh Aliyari, Wan-Xiang Li, Hong-Wei Li and Peter Atkinson of UCR; and Kevin Kim and Richard Carthew of Northwestern University, Ill., collaborated with Ding on the study which was funded by grants from the National Institutes of Health and the U.S. Department of Agriculture.

"Our work has implications for insects that vector viral disease," said Atkinson, a professor of entomology, who advised the research team on how RNA and viruses could be introduced to fly embryos and adults. "It introduces a new approach to perhaps make these insects more susceptible to the virus, thereby killing them before they have a chance to transmit the disease to an uninfected person."

The University of California, Riverside is a major research institution. Key areas of research include nanotechnology, genomics, environmental studies, digital arts and sustainable growth and development. With a current undergraduate and graduate enrollment of more than 16,600, the campus is projected to grow to 21,000 students by 2010. Located in the heart of Inland Southern California, the nearly 1,200-acre, park-like campus is at the center of the region's economic development. Visit www.ucr.edu or call 951-UCR-NEWS for more information. Media sources are available at http://www.mediasources.ucr.edu/.


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