that detects certain viruses
Yale researchers have identified an intruder-sensing system that hones in on single-stranded RNA viruses, such as influenza, according to a study published in the March 23 issue of the Proceedings of the National Academy of Sciences.
When a cell engulfs a virus, it must recognize the nature of the intruder. Viruses come in many genetic forms, including double-stranded RNA, single-stranded RNA or DNA. Toll-like receptors, which are part of the body's innate immune detection system, are embedded in the cellular membrane and respond only to specific motifs. When activated, the receptors stimulate elements that begin the defense cascade.
Akiko Iwasaki, assistant professor of epidemiology and public health and of immunobiology at the School of Medicine, and Richard Flavell, Sterling Professor of Medicine and chair of the Section of Immunobiology, and their colleagues found that mice selectively bred to lack the gene for toll-like receptor 7 (TLR7) were unable to produce a response against two different single-stranded RNA viruses.
Single-stranded RNA is a motif that is normally present in the cell, so the researchers were curious about how the cell differentiates the viral intruder from its own molecules. They found that activation of TLR7 requires an acid environment. This acid environment is only found inside endosomes, bubbles created when the cell engulfs the virus along with part of its own membrane. As the endosome travels into the cell, its interior becomes more acidic. When the authors added a chemical to the cells that prevents acidification, TLR7 failed to activate, despite the presence of single-stranded viral RNA.
"The results suggest that active engulfment is necessary for recognition of single-stranded RNA viruses," Iwasaki says.
Co-authors included Jennifer Lund, Lena Alexopoulou, Ayuko Sato, Margaret Karow, Niels Adams and Nicholas Gale.
-- By Jacqueline Weaver
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