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Could a Mystery Virus be the Culprit in Kawasaki Disease?


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In the Nature podcast interview that went along with my Kawasaki Disease story at Nature (look for the interview halfway down the page at the story here), I talked about the tantalizing work of Dr. Anne Rowley at the Northwestern Feinberg School of Medicine. She has studied the tissues of Kawasaki Disease patients and believes she has found virus-like particles in their respiratory tissues (hold tight for exciting photos at the bottom of this post). But in describing her research during the interview, I misspoke slightly (forgive me Anne! I was nervous!). Before I correct what I said, a little bit more about her work.

While reporting the KD story, I learned that Rowley was on the trail of a possible virus responsible for Kawasaki Disease from Dr. Jane Burns. I called Dr. Rowley to find out about that, and I found Anne’s work fascinating and included it in my first draft of the story. I was disappointed it didn’t make it into the final version of the story (again, for space reasons). So here’s her story, from the cutting room floor:

Anne Rowley, professor of pediatrics and microbiology/immunology at Northwestern University Feinberg School of Medicine, has been investigating the possibility that Kawasaki disease is caused by a virus.

Rowley has isolated antibodies from the immune cells infiltrating the coronary arteries of children who died from the disease. Her team made synthetic versions of these antibodies and incubated them with the tissues of children that had died of Kawasaki Disease, they found, to their surprise, that they bound to “inclusion bodies” in several of their tissues, including the cells lining the respiratory tract. Many respiratory pathogens – both bacterial and viral — make such inclusion bodies in the bronchial epithelium.

“It fit the hypothesis of a ubiqutious respiratory infectious agent that we were able to see these inclusion bodies in the bronchial epithelium,” she said.

When they looked at these inclusion bodies under electron microscopy, they found no sign of bacteria. But they did find both spherical and rod-shaped virus-like particles nearby.

“If you kind of put all that together you end up concluding the features are not compatible with any known virus family,” Rowley said. “So we suspect that it would represent a new virus family and we think that that’s why it’s been so difficult to identify the causative agent.”

Working with the viral genomics discovery group at Washington University in St. Louis, they are now looking for gene sequences in their tissue samples that have viral homology or that have no match. They hope to assemble the longest possible sequence prevalent among KD patients, and then test living Kawasaki patients to find out if their sequence turns up in those children.

What I meant to say during my interview — but did not in my nervous haze — was that Rowley had found virus-like particles associated with inclusion bodies in the lung tissues of Kawasaki victims. The virus-like particles were not the inclusion bodies themselves (which is what I said in the interview). Mea culpa.

As I mentioned above, the virus-like particles came in two different shapes: spherical and rod-shaped. In support of her hypothesis that the KD pathogen represents a new virus family, I’m not aware of any other virus with such a dimorphic appearance (Readers: Do you know of any? UPDATE: Anne informs me that the influenza virus itself can be di/pleomorphic. In addition to being spherical, it can also be filamentous! I had no idea! See this paper for some great images). But perhaps there are two separate viruses at work here? Or some other bizarre possibility? As with so many things Kawasaki, it’s impossible to say right now.

Here’s a photo showing the virus-like particles from KD patients from Rowley’s paper in the Journal of Infectious Disease last year (“Ultrastructural, immunofluorescence, and RNA evidence support the hypothesis of a “new” virus associated with Kawasaki disease.”). The arrows are pointing to the virus-like particles from Figs. 3 and 5.

Spherical (left) and rod-shaped (right) virus-like particles found in the tissues of Kawasaki victims. From Figs. 3C and 5C of J Infect Dis. 2011 Apr 1;203(7):1021-30. Click for link to paper.

Fascinating! It will be interesting to follow this study and find out if these particles indeed prove to be the culprit. And if so, to find out where these viruses are coming from, and how they survive that impressive trans-oceanic commute!

One other slight amendment: besides the Aspergillus disease of sea fans and Valley Fever in humans, there are two other diseases that are known to be windborne and remain infectious over distances of 1000-or-so kilometers, according to plant pathologist Don Aylor, who I also interviewed for the article: tobacco blue mold, and wheat stem rust, which are both fungal pathogens like Valley Fever and the Aspergillus sea fan disease. Neither of those two plant pathogens has ever been shown to cross an ocean.

Jennifer Frazer About the Author: Jennifer Frazer is a AAAS Science Journalism Award-winning science writer. She has degrees in biology, plant pathology/mycology, and science writing, and has spent many happy hours studying life in situ.
Nature Blog Network
Follow on Twitter @JenniferFrazer.

The views expressed are those of the author and are not necessarily those of Scientific American.





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