Immune system response to viral DNA is unique

The human body has a unique immune system response to foreign DNA, suggesting that DNA viruses and RNA viruses are detected by different mechanisms, Yale School of Medicine researchers report this week in Immunity.

The researchers also found that DNA recognition might be used to detect invasive bacteria in addition to viruses, according to Daniel Stetson, a post doctoral fellow in the Section of Immunobiology and lead author of the study.

Although there are countless types of viruses, they can all be placed in two categories based on the type of nucleic acids that comprise their genome: viruses made of RNA and viruses made of DNA. Infected cells sense the presence of foreign nucleic acids as viruses replicate inside them and distill the problem of recognizing a dizzying array of viruses into a relatively simple mechanism for turning on the immune response.

"It is well established that such a pathway exists for detection of viral RNA inside infected cells," Stetson said. "In contrast, very little is known about whether cells can detect foreign intracellular DNA or how this system might function."

Stetson and Ruslan Medshitov, professor of immunobiology, a Howard Hughes Institute investigator, and senior author of the study, compared the innate immune response to intracellular DNA with other virus recognition pathways.

"We found that this novel pathway seems to function differently from all other known nucleic acid sensors," Stetson said. "The unique immune response activated by foreign DNA suggests that DNA viruses and RNA viruses are detected by different mechanisms."

Stetson said one important question raised by these findings is how this newly described system avoids responding to genomic DNA that is contained within all cells.

"If this 'tolerance' to self DNA were to break down, cells might mount an antiviral response against their own DNA," he said. "Further characterization of this pathway will shed light on the mechanisms of antiviral responses and how cells discern viral and self-DNA."

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Immunity 24: pp 1-11 (January 2006)


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