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Avian mystery: Dermatologist solves viral puzzle, looks for human impact

Article

National report - Scott Karlene, M.D., a dermatologist in Flint, Mich., wasn’t planning to isolate and identify an avian virus that was killing parrots. But he did.

National report

- Scott Karlene, M.D., a dermatologist in Flint, Mich., wasn’t planning to isolate and identify an avian virus that was killing parrots. But he did.

And now he wonders if the avian bornavirus, which results in a fatal neuromotor disorder in some exotic birds, might cross species - and possibly even affect humans.

Michigan dermatologist and researcher Scott Karlene, M.D., sits at his microscope with his pet palm cockatoo, Squawky.Photo: Scott Karlene, M.D.

While Dr. Karlene admits that his theories are not yet backed by research, he wonders if the discovery of the bornavirus could help researchers better understand the role of viruses in dermatological and other disorders, such as lichen planus.


Started with birds

Dr. Karlene, a clinical professor, department of medicine, Michigan State University, practices dermatology and conducts self-funded research, with a special interest in finding the viral cause of disease.

He founded the Lahser Interspecies Research Foundation, a private foundation that provides funding for his and other research.

Aware of Dr. Karlene’s interest, the veterinarian who cares for his pet parrot, Squawky, asked if Dr. Karlene knew about proventricular dilatation disease, which affects some exotic birds.

The dermatologist hadn’t heard of the disease, which is characterized by lymphoplasmacytic infiltration of the ganglia of the central and peripheral nervous system. Afflicted birds experience central nervous system disorders, disordered enteric motility and associated wasting.

The veterinarian "said it is a fascinating disease because it parallels so many human diseases. It is similar in its clinical presentation to patients with Parkinson’s disease and inflammatory bowel disease," Dr. Karlene says.

Pulling the literature from the past 20 years, Dr. Karlene found that veterinarians had tried unsuccessfully to discover the cause of proventricular dilatation for some 20 years.

"The problem that I saw immediately was that they could not define the disease,&34; Dr. Karlene says.

Armed with access to specimens from dead birds, Dr. Karlene turned to Joseph DeRisi, Ph.D., of the University of California, San Francisco, who is known for having a sophisticated viral chip technology for viral identification.Finding a virus is a tedious process - and one that is unlikely to pan out, Dr. Karlene explains. But the UCSF research team was successful this time, identifying what Dr. Karlene and his colleagues have pegged "avian bornavirus," which had never been described before.

"The significance of this virus is most interesting," Dr. Karlene says.

A horse-related virus, bornavirus, in its original form, also has been shown to transmit to primates and other species. The bornavirus enters the body through nasal inhalation, then moves to the brain, where it causes a host of neuromotor problems.

Dr. Karlene is among the authors of a related paper published July 2008 in the Journal of Virology. His coauthors include Dr. DeRisi and Susan Clubb, D.V.M., a board-certified avian specialist in Loxahatchee, Fla.

The researchers recovered the complete viral genome sequence from one of the virus-positive specimens, revealing a bornavirus-like genome organization much different than that of prior bornavirus isolates.

Dr. Clubb wonders whether the finding might have implications for some avian dermatology issues, such as feather plucking and skin mutilation in parrots. It helped, she says, to have a multidisciplinary team cracking the mystery of proventricular dilatation disease.

"It is always good to have another opinion, especially someone who looks at things from a totally different point of view," Clubb says. She says the experience taught her "to never stop looking. Keep an open mind and do not give up."


Human connection?

Dr. Karlene will launch studies in 2009 looking at whether the avian birnavirus crosses species lines, as well as whether the virus is a public health threat.

He plans to tap neurology colleagues to study a potential connection among viruses, immune suppression and neurological illnesses. Some of that work could hit home for dermatologists, he says.

For example, Dr. Karlene says physicians used to see progressive multifocal leukoencephalopathy, which is caused by central nervous system infection by group B human papovaviruses, predominantly in AIDS patients. Now the disease is turning up in patients who are on biological treatment agents in dermatology.

"The question is, what happens when we are using these agents in ways that suppress the immune system in the long term?" he says.

In addition to doing more research on potential human implications of the avian bornavirus, Dr. Karlene hopes to study his theory that there might be a viral connection with keratoacanthoma and lichen planus.

"Many of the diseases that we face are probably related to undiagnosed viruses. As traditionally trained medical doctors, we have heard about viruses causing disease for a long time, but we never really had the technology to identify these viruses … until just recently," he says. "As dermatologists, we see pityriasis rosea or lichen planus and we tend to think these things are reactions to infections.

"Today, there is the thinking in very sophisticated circles that these diseases are actually caused by the viruses themselves. So, we are ramping up our efforts to determine the exact etiology, whether it be viral or genetic or other.

"Another example: In the past several months, a polyoma virus, which is very common in different strains in birds, has been implicated in the pathogenesis of Merkel cell tumors."

Clearly, he says, dermatologists need to arm themselves with such information as they turn more and more to immunosuppression agents as treatment for skin disease.

Dr. Karlene’s partner, dermatologist Kevin Gaffney, M.D., thinks his colleague is onto something big.

"[His research] will help medicine, in general, in that this research will hopefully elucidate many ways in which chronic diseases that we do not understand may be related to infectious causes, such as viral infection," Dr. Gaffney says.

"There are many diseases that we see in dermatology that we have no good explanation for. It could be that many of these are related to common viruses in our environment that we acquire and probably clear - the acute infection - but ultimately [we] are left with these immune issues that result in diseases." DT

Disclosure: Dr. Karlene founded the Lahser Interspecies Research Foundation, a private foundation that provides funding for his and other research.

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