A picture is worth a thousand words for understating innate immunity

by Tom Ulrich on January 18, 2013

What you're looking at is one of the key ways in which our immune system recognizes viruses before they cause trouble: by sensing the physical presence of their genes. This image by Sun Hur, PhD, will help us better understand how.

Our immune system has immense powers of observation. It needs to in order to fend off the millions of bacteria, viruses, fungi, you name it, that we get exposed to every day.

I’m not talking about antibodies and T cells—parts of the immune system’s adaptive arm, which is fine-tuned to recognize a specific virus or bacterium. Rather, I’m talking about pattern recognition proteins—biological sensors capable of recognizing features and structures that only bacteria or viruses have. These make up the immune system’s innate arm, which essentially primes the body to attack anything that looks remotely like it doesn’t belong.

For instance, our cells carry sensors that can detect double-stranded RNA (dsRNA), which certain kinds of viruses use to encode their genome—like the rotavirus, which causes severe diarrhea in infants and small children. Our genome, by contrast, is encoded in DNA, and the RNA we make is single-stranded; if there’s dsRNA present, it means there’s a virus around.

In a recent paper in Cell, Sun Hur, PhD, of the Program in Cellular and Molecular Medicine at Boston Children’s Hospital, and one of her postdoctoral fellows, Bin Wu, PhD, spotlight one of our dsRNA pattern recognizers, a protein called MDA5. Hur has studied MDA5 for a couple of years as part of her overall research on how the body distinguishes, at a molecular level, what is “self” and “non-self” and efficiently triggers the right kind of immune response.

Hur used a technology called x-ray crystallography to work out how MDA5 forms filaments or tubes that wrap around and bind to dsRNA. The results give us more detail about the machinery cells use to find viruses and call in help from the rest of the immune system before any damage is done.

When you think about the shape of MDA5, think Life Savers. (amanda_munoz/Flickr)

“MDA5 is shaped like a Life Savers candy,” explains Hur, who is also part of Harvard Medical School’s Department of Biological Chemistry & Molecular Pharmacology. “What we discovered is that individual MDA5s stack on top of each other to form a filament that wraps around a length of dsRNA. The length of the filament tells the cell how long the dsRNA is, which helps confirm whether it is indeed from a virus.”

Hur also notes that adjacent MDA5s, in a filament position themselves such that their signaling domains—the sections of MDA5 that interact with other proteins in the cell to trigger an immune response—are very close together. “That allows the proteins to strongly alert the rest of the cell that viral dsRNA is present, and activate anti-viral immune activity.”

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