US develops lethal new viruses (29 October 2003)

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US develops lethal new viruses

 

19:00 29 October 03

 

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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 no 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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For more related stories

search the print edition Archive

 

 

 

Weblinks

 

Mark Buller, University of St Louis

 

Ian Ramshaw's group, Australian National University

 

Bioterrorism, New Scientist