Sunday, April 27, 2008

UCSF researchers identify virus behind mysterious parrot disease

Researchers at the University of California, San Francisco, have
identified a virus behind the mysterious infectious disease that has
been killing parrots and exotic birds for more than 30 years.

The team, led by UCSF professors Joseph DeRisi, PhD, and Don Ganem,
MD, also has developed a diagnostic test for the virus linked to
Proventricular Dilation Disease, or PDD, which will enable
veterinarians worldwide to control the spread of the virus.

Results of the study will be published in “Virology Journal” and will
appear online in August. The findings also will be presented in full
at the August 11 annual meeting of the Association of Avian
Veterinarians, in Savannah, GA.

The new virus, which the team named Avian Bornavirus (ABV), is a
member of the bornavirus family, whose other members cause
encephalitis in horses and livestock. Working with veterinarians on
two continents, the group isolated this virus in 71 percent of the
samples from infected birds, but none of the healthy individuals.

“This discovery has potentially solved a mystery that has been
plaguing the avian veterinary community since the 1970s,” said DeRisi,
a molecular biologist whose laboratory aided in the 2003 discovery of
the virus causing Severe Acute Respiratory Syndrome, or SARS, in
humans. “These results clearly reveal the existence of an avian
reservoir of remarkably diverse bornaviruses that are dramatically
different from anything seen in other animals.”

The discovery could have profound consequences on both domesticated
parrots and in the conservation of endangered species, according to
DeRisi and Ganem, both Howard Hughes Medical Investigators at UCSF.
Those species include the Spix’s Macaw, currently one of the most
endangered birds in the world, whose number has dwindled to roughly
100 worldwide and whose continued existence is threatened by PDD.

The research was spearheaded by Amy Kistler, a postdoctoral fellow in
the DeRisi and Ganem labs. Together with veterinarians Susan Clubb, in
the United States, and Ady Gancz in Israel, Kistler analyzed affected
birds using UCSF’s patented ViroChip technology.

The ViroChip, which DeRisi and Ganem developed, is a high-throughput
screening technology that uses a DNA microarray to test viral samples.
The team was able to recover virus sequence from a total of 16
diseased birds from two different continents. The complete genome
sequence of one isolate was captured using ultra deep sequencing.

The virus they identified is highly divergent from all previously
identified members of the “Bornaviridae” family and represents the
first full-length bornavirus genome ever cloned directly from avian
tissue. Analysis of the Avian Bornavirus genome revealed at least five
distinct varieties.

PDD is a fatal disease that causes nervous system disorders in both
domesticated and wild birds in the psittacine, or parrot, family
worldwide. The disease has been found in 50 different species of
parrots, as well as five other orders of birds, and is widely
considered to be the greatest threat to captive breeding of birds in
this family, the researchers said.

The disorder often leads to the birds’ inability to swallow and digest
food, with resulting wasting; many birds also suffer from neurologic
symptoms such as imbalance and lack of coordination. Regardless of the
clinical course the disease takes, it is often fatal.

Scientists have theorized for decades that a viral pathogen was the
source of the disease, but until now, no one had been able to identify
the likely culprit.

“This provides a very compelling lead in the long-standing search for
a viral cause of PDD,” Ganem said. “With the development of molecular
clones and diagnostic tests for ABV, we can now begin to explore both
the epidemiology of the virus and how it is linked to the disease

Co-authors on the paper include Amy L. Kistler, Peter Skewes-Cox, Kael
Fisher, Katherine Sorber, Charles Y. Chiu and Alexander Greninger,
from the Howard Hughes Medical Institute and Department of
Biochemistry, Microbiology and Medicine at UCSF; Ady Gancz, from The
Exotic Clinic, Herzlyia, Israel; Susan Clubb, Rainforest Clinic for
Birds and Exotics, Loxahatchee, Fla.; Avishai Lublin, Sara Mechani and
Yigal Farnoushi, of the Division of Avian and Fish Diseases, Kimron
Veterinary Institute, bet Dagan, Israel; and Scott B. Karlene, of the
Lahser Interspecies Research Foundation, Bloomfield Hills, MI.

The research was supported by funding to DeRisi and Ganem from the
Howard Hughes Medical Institute and the Doris Duke Charitable
Foundation. Funding for US specimen collection and veterinary care was
provided by the Lahser Interspecies Research Foundation.

The DeRisi Laboratory is part of the California Institute for
Quantitative Biosciences, known as QB3, a cooperative effort among
private industry and more than 180 scientists at UCSF, UC Berkeley and
UC Santa Cruz. The collaboration harnesses the quantitative sciences
to integrate and enhance scientific understanding of biological
systems at all levels, enabling scientists to tackle problems that
have been previously unapproachable.

UCSF is a leading university dedicated to promoting health worldwide
through advanced biomedical research, graduate-level education in the
life sciences and health professions, and excellence in patient care.
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