Animal to human mutation of virus often a simple step

3/23/2003

In 1988, thousands of Atlantic seals died in an outbreak of a distemperlike virus. In 2002, thousands more fell prey to a second round that threatened to wipe out half the population of gray and common seals. A similar distemper epidemic struck lions in the Serengeti in 1993-94.

In 2002, 103 people died in an outbreak of Nepa Virus. Nearly 300 people in Singapore and Malaysia were infected. All lived around pigs. In Australia, a virus in horses killed two trainers who worked with them. Today, at least 10 people are dead and 350 others infected with a virus world health workers are calling Severe Acute Respiratory Syndrome. Researchers think they may have a handle on the culprit behind SARS. It appears to be of the same family that killed seals and lions, and moved from pigs and horses to humans: the paramyxoviruses.

These stories of paramyxovirus epidemics are frightening. But perhaps more disquieting is this: These are the close relations of our childhood companions - chickenpox, measles, and mumps. These are treatable. It is not unheard of for mothers purposely to take a preschooler to the home of a playmate with a paramyxovirus, simply to get chickenpox out of the way. But these tamed varieties - although measles outbreaks in unvaccinated populations are quite capable of killing - allowed us to forget just how utterly pliable a virus can be in the right setting. Often that setting is a place where animals and humans mix, says Stanley G. Sawicki, a virologist at the Medical College of Ohio.

This flexibility stems, in a large part, from the nature of viruses. Viruses are little genetic instruction sets waiting to be carried out. What is critical here is that paramyxoviruses, such as influenza viruses, are poor copiers. There is no spell-checking and no repair. Their offspring are often full of errors, says Dr. David Mindell, a professor of ecology and evolutionary biology at the University of Michigan.

“They need to have lots of progeny,” because many won't survive the bad editing, he says. Yet the ones that live can win accidental benefit from this low-fidelity process. The significance of even a single error can be heart-stopping.

Take an influenza outbreak that occurred in 1997.

The World Health Organization keeps close watch for emerging flu types in order to ensure yearly vaccine formulations keep up with viral evolution. The influenza strain that showed up in Hong Kong in 1997 had all the hallmarks of big trouble. It jumped from chickens to humans and killed its victims. A mutation allowed it to evade the body's initial defenses.

Quick action to kill more than a million domestic fowl prevented human disaster. Only six people died in the outbreak because the virus hadn't learned to move from human to human, only animal to human. Had it gained a foothold in humans, it may have easily evolved to close that final gap in our defenses.

A single mutation made it deadly, reports Robert G. Webster, a virologist from St. Jude's Children's Research Hospital in Memphis in a recent issue of American Scientist. The influenza virus has eight genes made up of a few thousand nucleotides. A change in a single nucleotide endowed this influenza strain with murderous capabilities.

What contributes to the mutability of paramyxoviruses and influenza may be the hosts in which they land. In influenza, the pattern is well known. The virus lives in waterfowl without causing disease. But when waterfowl mix with domestic animals, the virus can jump species. In China, where poultry, pigs, and people live in close proximity, it's an easy set of steps. Pigs make ideal cauldrons for virus brewing. The animal's cells carry receptors for both bird and human viruses. When viruses from both species meet inside a pig cell, they may swap genes. The result is a new viral form fit for humans.

Such species mixing may have played a role in the SARS virus. “Any time you have intimate contact between animals and people,” there's a chance for new combinations with new virulence,” says Michael Lairmore, who studies viruses at The Ohio State University.

Increased human exposure to animals increases the risk, he says. For instance, increased human exposure to chimpanzee viruses led to AIDS. Add to this the ease of international travel, and outbreaks such as SARS seem like the coming trend.

“The more worldwide movement of people you have, the more population density you have, the easier it is for the disease to move,'' says Dr. Susan McLellan, a tropical medical specialist at Tulane University in New Orleans. “We have to improve surveillance. It makes it easier to realize when these things are occurring,” she says.