Pest solution goes back for mouse-to-mouse resuscitation

Plans to conduct the first contained field trial of a transgenic virus designed to prevent episodic plagues of the house mouse in the Australian wheat belt have been set back while researchers work to improve its transmission under field conditions.

The transgenic virus has been returned to the laboratory for a little mouse-to-mouse resuscitation, amid concerns that it has become too domesticated to spread efficiently in the early phases of Mus domesticus plagues.

Dr David Dall, CEO of Pestat, the company established to commercialise the anti-fertility technologies being developed by the Cooperative Research Centre for Pest Animal Control (CRCPAC), has asked the CRC to engineer a more infectious strain of the virus.

After years of laboratory research, the transgenic mouse cytomegalovirus (MCMV) virus appears to have lost its punch because of the phenomenon of attenuation -- a phenomenon commonly exploited to produce weakened virus strains for vaccines.

In essence, the virus has been selected for its ability to replicate in the laboratory, not for its ability to be transmitted between infected and healthy mice.

The virus induces 100 per cent sterility when injected, by inducing the female's immune system to mount an antibody attack on a key protein in zona pellucida, the jelly-like coating around the unfertilised egg.

But while the injected virus still induces 100 percent sterility, the latest data from laboratory tests indicates transmission is less efficient by the natural route. The current strain may not achieve the high levels of transmission required to defuse an incipient plague in its early stages.

"We recognise that the OGTR considers applications for field trials on a risk-benefit basis, and the benefit here relies on a high level of transmissibility," Dall said.

"Realistically, our application to the OGTR to conduct the first contained field trial has been pushed back to the middle of next year."

Dall said CRCPAC researchers would go back to the original isolate of the wild-type virus, strain 64, from a mouse in Geraldton, WA, to see if the current strains held in the laboratory have escaped attenuation.

They will also try to isolate new variants from mice in the eastern states. "It's very widespread in mice in the field, so it's not hard to find," he said.

"Once we have established it in laboratory mouse-cell cultures, the idea is to passage it as few times as possible, so we're not selecting for any characteristics other than those required for high levels of transmission in the field."

Dall said Pestat and the CRC were "still as confident as we can be" that the technology, called virally vectored immunosterilisation, will work when it is eventually deployed.

Asked if the attenuation problem should have been foreseen, Dall said, "Until very recently the emphasis was put on making it work in inoculated mice, and getting proof of concept, as the culmination of many years of work.

"The people doing the work would argue that there's not much point worrying about transmissibility until you have obtained proof of concept."