Deadly virus effortlessly hops species

Genetic engineering helps reveal origin of deadly 'flu

2 April 2003

HELEN PEARSON

SARS coronavirus might have arisen when an animal and human virus met and swapped genes. © GettyImages

A single genetic change could have created the deadly virus that has killed over 50 people and infected more than 1,600, a new study suggests.

A new type of coronavirus is thought to be behind the pneumonia-like disease dubbed severe acute respiratory syndrome (SARS). Now, in a simple overnight experiment, researchers transformed a coronavirus that is lethal to cats into one that infects mouse cells by replacing a single gene¹.

The result strengthens the idea that the SARS coronavirus might have arisen when an animal and human virus met and swapped genes, says the study's lead scientist, Peter Rottier of Utrecht University in the Netherlands. "It's a very plausible explanation," he adds.

Rottier's team created the new coronavirus by injecting cat cells with feline infectious peritonitis virus (FIPV), a common pathogen that kills around 5% of cats. The researchers added a gene fragment from a mouse coronavirus; this makes a coat protein that recognizes and helps to penetrate mouse cells.

After several hours, some particles of the cat virus had exchanged their coat gene for the mouse one - and could then infect mouse cells. This is analogous to what might happen if the two viruses simultaneously infected the same cell.

Coronaviruses are unusual in their ability to reshuffle genes easily in this way, explains Michael Lai of the University of Southern California in Los Angeles, who works on them. The study shows that the viruses "can easily switch their host range by switching genes", he says.

The SARS virus might also have arisen when an existing animal or human coronavirus mutated into a more deadly form, says Lai. Which of these explanations is true will become clear when the full genetic sequence of the virus is pieced together, possibly this week.

Rottier's team is already producing live vaccines against coronaviruses, using the same technique. They screened the strains of FIPV that infect mice for those that had become innocuous in the genetic reshuffle. Vaccination with one of these strains protects cats from the original, lethal FIPV, they found.

In theory, bioterrorists could abuse this genetic transformation procedure to turn an animal coronavirus into a dangerous human pathogen such as that responsible for SARS. But this and other similar virus-altering techniques are not new, say experts. For example, in 2000, the team used the same method to engineer a mouse coronavirus that infects cats.

"The only way we'll ever understand these natural outbreaks is by first-rate science and getting it published," says Lynn Enquist, editor of the Journal of Virology, where the latest work was published.

1. Haijema, B.J., Volders, H. & Rottier, P.J.M. Switching species tropism: an effective way to manipulate the feline coronavirus genome. Journal of Virology, 77, 4528 - 4538, (2003). |Article|