US develops lethal new viruses

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http://www.newscientist.com/news/news.jsp?id=ns99994318

 

 

US develops lethal new viruses

19:00 29 October 03

A scientist funded by the US government has deliberately created an extremely

deadly form of mousepox, a relative of the smallpox virus, through genetic

engineering.

 

The new virus kills all mice even if they have been given antiviral drugs as

well as a vaccine that would normally protect them.

 

The work has not stopped there. The cowpox virus, which infects a range of

animals including humans, has been genetically altered in a similar way.

 

The new virus, which is about to be tested on animals, should be lethal only to

mice, Mark Buller of the University of St Louis told New Scientist. He says his

work is necessary to explore what bioterrorists might do.

 

But the research brings closer the prospect of pox viruses that cause only mild

infections in humans being turned into diseases lethal even to people who have

been vaccinated.

 

And vaccines are currently our main defence against smallpox and its relatives,

such as the monkeypox that reached the US this year. Some researchers think the

latest research is risky and unnecessary.

 

" I have great concern about doing this in a pox virus that can cross species, "

said Ian Ramshaw of the Australian National University in Canberra on being told

of Buller's work.

 

Ramshaw was a member of the team that accidentally discovered how to make

mousepox more deadly (New Scientist, 13 January 2001). But the modified mousepox

his team created was not as deadly as Buller's.

 

 

No rebound

 

 

Since then, Ramshaw told New Scientist, his team has also created more deadly

forms of mousepox, and has used the same method to engineer a more deadly

rabbitpox virus.

 

But this research revealed that the modified pox viruses are not contagious, he

says. That is good news in the sense that these viruses could not cause

ecological havoc by wiping out mouse or rabbit populations around the world if

they escaped from a lab.

 

However, this discovery also means some bioterrorists might be more tempted to

use the same trick to modify a pox virus that infects humans. Such a disease,

like anthrax, would infect only those directly exposed to it. It would not

spread around the world and rebound on the attackers. But there is no guarantee

that other pox viruses modified in a similar way would also be non-contagious.

 

Ramshaw's team made its initial discovery while developing contraceptive

vaccines for sterilising mice and rabbits without killing them. The researchers

modified the mousepox virus by adding a gene for a natural immunosuppressant

called IL-4, expecting this would boost antibody production.

 

Instead, the modified mousepox virus was far more lethal, killing 60 per cent of

vaccinated mice. The addition of IL-4 seems to switch off a key part of the

immune system called the cell-mediated response.

 

 

Maximised production

 

 

Now Buller has engineered a mousepox strain that kills 100 per cent of

vaccinated mice, even when they were also treated with the antiviral drug

cidofovir. A monoclonal antibody that mops up IL-4 did save some, however.

 

His team " optimised " the virus by placing the IL-4 gene in a different part of

the viral genome and adding a promoter sequence to maximise production of the

IL-4 protein, he told a biosecurity conference in Geneva last week.

 

Buller has also constructed a cowpox virus containing the mouse IL-4 gene, which

is about to be tested on mice at the US Army Medical Research Institute of

Infectious Diseases at Fort Detrick, Maryland.

 

Cowpox infects people, but Buller says the IL-4 protein is species-specific and

would not affect the human immune system. The experiments are being done at the

second-highest level of biological containment.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Nine-eleven

 

 

Ramshaw says there is a reason to do the cowpox experiments, as his group's work

on rabbits has already shown the method works for other pox viruses. While

viruses containing mouse IL-4 should not be lethal to humans, recombinant

viruses can have unexpected effects, he says. " You'd hope the combination

remains mouse-specific. "

 

Why his group's engineered viruses are not contagious is a mystery, he says. It

is not, for instance, because the host dies faster than usual, taking the virus

with it. But his findings could explain why pox viruses containing IL-4 have

never evolved naturally, even though the viruses frequently pick up genes that

affect their host's immunity.

 

Despite the concerns, work on lethal new pox viruses seems likely to continue in

the US. When members of the audience in Geneva questioned the need for such

experiments, an American voice in the back boomed out: " Nine-eleven " . There were

murmurs of agreement.

 

Debora MacKenzie, Geneva

 

 

 

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