SARS: Behind the scenes

Severe acute respiratory syndrome, or SARS, has put respected virologists like David Brian, DVM, in touch with his human medical peers.

Mystified by SARS, physicians have just begun to tap the resources ofthe veterinary community who practically wrote the primer on coronavirus­ the reported cause of SARS.

One of the nation's leading authorities on bovine coronaviruses, Brian,of the University of Tennessee's College of Veterinary Medicine, says SARSgave the coronavirus much-needed publicity.

"To be honest, there hasn't been a whole lot of interest in thehuman medical community about coronaviruses until now, because not too manypeople die from the common cold (which belongs to the coronavirus family),"he says.

A much deadlier strain of the coronavirus, outbreaks of SARS have grippedAsia and Canada since mid-March, claiming thousands of lives. The UnitedStates remains spared of fatalities by the disease that causes respiratoryinfection in humans.

The veterinary side of medicine has been acutely aware of the potentialfor more devastating coronavirus strains. Coronaviruses are a common causeof mild to moderate upper-respiratory illness in humans and are associatedwith respiratory, gastrointestinal, liver and neurologic disease in animals.

"Veterinarians have known for a long time that coronaviruses cancause very, very nasty diseases," says Brian, who's collaborating withthe Centers for Disease Control and Prevention (CDC) on SARS research. "We'veoften said if anything ever happened in humans that would mimic any of thesediseases in animals - pigs, cats, chickens or cattle - it would be a majorpublic health problem. Here it is."

On the frontlines

When the CDC received the SARS virus isolate, they immediately contactedall who were working on coronaviruses to initially help identify the virus.Brian was one of dozens of recruits to a CDC coronavirus working group,since he worked heavily with bovine coronavirus.

CDC requested his lab and numerous others to send agents that would helpsequence the genome and definitively confirm it was a coronavirus.

Secondly, they wanted to establish its origin.

Thirdly, Brian says they intend to design a sequence-based diagnostickit for standardized application in the United States, if not the world,to prevent spread of disease.

On the sidelines

Gus Kousoulas, Ph.D., a virologist in Louisiana State University's Collegeof Veterinary Medicine, is also indirectly contributing to CDC's pool ofSARS research. Similar to Brian, he and recently retired veterinary clinicianDr. Hans Storz, also of LSU, have partnered for years on bovine coronavirusresearch.

"Respiratory bovine coronaviruses are the first description of SARSin large animals, like cattle. We're not surprised that the SARS coronaviruscan cause acute respiratory disease and pneumonia because we have seen itin cattle.

"By far a lot of the human medicine people have missed the cattlestory, which is really interesting. I joke sometimes with local news thatI could take some published work on bovine coronaviruses and replace (theword) cattle with human beings as well as a few other words and probablydescribe SARS."

His team was first to isolate coronaviruses from the respiratory tractsof cattle and were surprised to find these viruses infected the upper andlower respiratory tract of cattle.

Additionally, he and Storz published a paper where they isolated whatresembled a bovine coronavirus from acute diarrhea specimens from a 6-yearold in Germany.

"We found quite some time ago that quite a number of people in ruralconditions often had antibodies against bovine coronavirus," says Storz.

"Now, some medical schools are interested to compare what we'vefound in these fatal cases in cattle and what is emerging in human infection."

Such research mounts speculation as to whether the coronavirus jumpedspecies.

Emerging disease odds

The compact living arrangements of populations such as the Chinese arepotential breeding grounds for what Kousoulas calls hybrid viruses.

"In China you have chickens and birds and cattle and feces of humanbeings basically living in the same 10 square meters. That becomes a veryopportunistic environment for having hybrid viruses - recombinant viruses- created, very quickly."

In veterinary medicine there are dozens of examples of how viruses becomemore virulent as a result of jumping from one species into another or emergingas a new mutant virus.

Selecting a virus found in animals that can ultimately and successfullyinfect humans and cause disease is "just a matter of chance,"says Kousoulas.

Future plans

At UT, Brian insists his lab's work on coronaviruses has really onlyjust begun.

"We need to isolate more coronaviruses in wild animals worldwide;do more sequencing of those genomes to see if there's a reservoir of genesthat might explain the origin of SARS," he says.

Additionally, Kousoulas' lab has requested the genes of SARS to considerthe possibility of producing vaccines. He has secured a USDA grant to studythe genetics of respiratory bovine coronaviruses.

Prospects for coronavirus experts have never looked healthier.

"I think CDC is going to be interested in helping coronavirus virologistsfind new coronaviruses," says Brian. "Even for known coronaviruses- canine and feline coronaviruses, a new horse coronavirus that has beenisolated in North Carolina - we don't know the full genome sequences ofthese viruses yet and some of these diseases have been known for 25 years.

"But now, to better explain SARS, I think we're going to be ableto get funds to sequence the genomes of all coronaviruses."

New era

It's taken an outbreak of grave magnitude, particularly in Asia, to forgea tighter collaboration of professionals devoted to animal and human medicine.

"We are promoting veterinary medicine as a tool for medicine asa whole," says Kousoulas. "We receive diseases here in the veterinaryschool that (most) people don't know about. I think the coronavirus storyis just one of the stories."

The path to better medicine in the future may well be paved with veterinariansand human doctors.

Kousoulas adds, "The new era is that medicine is really medicine."