Pox parts list published

Inventory of vital smallpox virus genes offers hope not threat.
18 June 2003

HELEN PEARSON

Smallpox shares 90 genes with 20 other pox viruses. © SPL

Ninety genes are all it takes to build a primitive version of a virus like smallpox or monkeypox, shows a new study. The catalogue could help the search for drugs and vaccines.

A comparison of the sequences of 21 different poxviruses revealed the essential genes that they share¹. The 90 genes equip the viruses to infect and multiply in cells.

The parts list could enable someone to piece together a new, pared-down poxvirus, says group leader Rachel Roper at the University of Victoria, Canada. The idea of creating a virus from scratch became reality in 2002, when US researchers built a poliovirus from mail-order chemicals².

But experts say that the study is unlikely to help bioterrorists build a new, more dangerous version of smallpox.

For one thing, manufacturing even a poxvirus pared-down from the full 200,000 chemical blocks is far more challenging than building the 7,500-block poliovirus, says Eckard Wimmer of the State University of New York, Stony Brook, whose team assembled the poliovirus. "It's really a very laborious task," he says.

What's more, a virus built from just 90 genes "would be pretty wimpy," says poxvirus expert Richard Moyer of the University of Florida, Gainesville. A killer version would need extra genes to make it virulent, and researchers are not yet sure what these are, he says.

Instead, the hope is that the latest study will help tackle poxviruses. Although smallpox, the most fearsome in the family, was wiped out by vaccination, the hunt for better vaccines and cures continues amid fears that remaining stocks might be used as a bioweapon.

Target practice

This month's US outbreak of smallpox's milder cousin, monkeypox, has served as a reminder of the threat. Over 80 people are suspected of having been infected, mainly from pet prairie dogs that picked up the virus when housed with a Gambian giant rat imported from Africa. Patients suffer fever and a rash.

Vaccination remains the main weapon against smallpox, and is currently recommended for those suspected of exposure to monkeypox in the US. But because the vaccine is a mild, live poxvirus, it kills around 1 or 2 in a million people, and causes serious side effects in around 1 in a thousand.

A weak virus made from the 90 genes might make a better vaccine. The genes also offer obvious targets against which to aim new antiviral drugs, says virologist Mark Buller at the University of St Louis, Missouri: "One would expect you'd choose one of these."

A chemical that disabled a protein made by an essential gene, for example, might make a one-size-fits-all drug that could kill the entire virus family. One of the only antiviral drugs available against smallpox, called Cidofovir, already targets such a protein, but it has to be injected and can cause kidney problems.

Roper and her colleagues have compiled the poxvirus genome sequences from insects, camels, pigs and other animals into a publicly accessible database to help the hunt for drugs and vaccines. They have also found 15 genes carried by smallpox but not by monkeypox, which might explain why the former spreads more easily.

1. Upton, C., Slack, S., Hunter, A. L., Ehlers, A. & Roper, R. L. Poxvirus orthologous clusters: towards defining the minimum essential poxvirus genome. Journal of Virology, 77, 7590 - 7600, (2003). |Article|
2. Cello, J., Paul, A. V. & Wimmer, E.Chemical synthesis of poliovirus cDNA: generation of infectious virus in the absence of natural template. Science, published online, doi:10.1126/science.1072266 (2003). |Article|