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| Courtesy of kabils / www.flickr.com/creativecommons |
On their own, the symptoms don't sound deadly: despondence, weight loss, fatigue. But after a few months, or in some cases a few years, all birds with proventricular dilatation disease (PDD) wind up dead. PDD began appearing in veterinary clinics in the 1970s. It eventually spread to parrots worldwide, and can easily wipe out an entire colony.
From the beginning, veterinarians suspected PDD had viral causes. Then, a few years ago, a parrot owner suggested that his veterinarian contact Joseph DeRisi's lab at University of California, San Francisco (UCSF). DeRisi had made a name for himself by coinventing the ViroChip, a microarray chip that contains conserved genetic sequences from all known viruses. The array identifies new viruses when they are related closely enough to a known virus family to cross-hybridize with the probes on the chip. In 2003, DeRisi and his former colleague David Wang used the chip to identify the SARS virus. DeRisi had never heard of PDD, but he was intrigued by the cases the veterinarian described.
Always eager to take on the challenge of identifying a new virus, in December, 2006, DeRisi and postdoc Amy Kistler used the ViroChip to analyze samples from the veterinarian and from a group in Israel who had recently experienced an outbreak of PDD. "One thing that's really nice about the microarray is the cross-hybridization," says Kistler. "With PCR, if you have mutations or mis-senses in your sequence, particularly in the 3' end, those primers might not work, whereas with the array we can tolerate almost a 50% mismatch. It's a much more sensitive tool compared to directed PCR." In this case, DeRisi and Kistler really needed that sensitivity: the virus they discovered was so divergent from its mammalian relatives, it never would have shown up with traditional PCR.
Researchers had speculated in earlier reports that the virus behind PDD might be a type of paramyxovirus, the virus that causes measles and mumps, or the herpes virus, since studies had shown both viruses could infect birds. But the results from the ViroChip showed a much more unexpected culprit: bornavirus, a highly-conserved virus thought to infect only mammals, particularly horses and donkeys. "Previously, bornavirus was thought of just as 'sad horse disease'," DeRisi explains, referring to the wasting disease first described in Central Europe in the 19th century, which also involves weight loss and depression.
But the avian bornavirus DeRisi and Kistler isolated in the lab bore little resemblance to the known mammalian varieties; the avian virus had less than 70% sequence identity to the known mammalian sequences. Plus, rather than one conserved sequence, they found five highly divergent variants. "It makes sense that eventually someone would find divergent bornaviruses, but who would have thought it would be in parrots?" says DeRisi. "So now you've got horses and parrots, but where's all the stuff in the middle? That's the part that's very exciting. It implies the bornavirus family is much larger in scope [than previously believed]."
DeRisi and Kistler published their findings in Virology Journal last July (Virol J, 5:88, 2008). Then, a few months later, their discovery was reinforced when a group at Columbia University published similar results using a different set of birds. "It's really very interesting and exciting," says Juan Carlos de la Torre, a bornavirus expert at the Scripps Research Institute in La Jolla, Calif. "So far, we thought bornavirus was only infecting mammals. This definitely raises some issues in the field." For instance, the high amount of genetic variation suggests that bornavirus has been evolving in birds for a long time, possibly longer than it has been in mammals.
Meanwhile, Kistler has been working to understand the basic biology of the virus by expressing it in avian cell lines and mapping virus transmission in a local parrot flock that contains both healthy and infected birds.
As for DeRisi, someone recently sent him an email about a frog species that appears to be dying off due to an unknown virus, so he might pursue that project next. "Whatever it may be, if there's a biology mystery with an infectious disease component, I'm game," he says.
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