Creation of a killer poxvirus

22 May 2008

Nearly one-third of the budget for the National Institute of Allergy and Infectious Diseases, an institute of the National Institutes of Health, goes towards research on bioterrorism. The concern is that pathogenic viruses, bacteria, and other microorganisms might be used in terrorist attacks, and therefore research is required to produce suitable vaccines and drugs.

Whether or not we should be worried about bioterrorism is an important question. I am of the opinion that the outcome of bioterrorism is so unpredictable that it probably falls very low in the terrorist’s arsenal. Nevertheless, it is worthwhile to consider all facets of this problem, which I intend to do over the coming weeks.

A common fear is that genetic engineering will be used to create even more lethal viruses than already exist. I believe this is highly unlikely for a number of reasons. First, no one knows how to make a virus more virulent for humans yet maintain its ability to be efficiently transmitted – a key property. Insertions of foreign genes into viral genomes is likely to reduce their ability to replicate and have an adverse effect on disease. While virologists may have many ideas about how to improve the virulence of viruses, it is highly unlikely that such viruses would do well in humans.

There is one well known example of the creation of a more virulent virus that bears discussion. In an attempt to reduce a wild rodent infestation in the late 1990s, Australian scientists decided to genetically engineer ectromelia virus, a member of the Poxviridae. The idea was to introduce into the viral genome the coding region for a mouse egg protein; upon infection of mice, the animals would mount an antibody response against the protein that would destroy eggs in female mice. In first tests the mice did not mount a good antibody response against the egg protein; therefore it was decided to incorporate the gene encoding interleukin-4 (IL-4) into the recombinant virus. This decision was based on the observation that IL-4 boosts antibody production in mice, and might increase the antibody response against the egg protein.

When the recombinant virus was injected into mice, it replicated out of control, killing the animals. Even mice that were immune to the parent ectromelia virus could not combat infection with the recombinant virus. The researchers were shocked, and debated whether it would be prudent to publish their findings. They eventually did, in the Journal of Virology.

Although this is a chilling incident, I believe that such a virus would not fare well if introduced into wild mouse populations. I suspect that the insertion of foreign genes (encoding the egg protein and IL-4) would reduce the growth of the virus so that it would no longer effectively spread among mice. While the virus is virulent when injected into mice in the laboratory, in nature, it would be unlikely to spread among mice.

There are other reasons to believe that such engineered viruses would not do well in nature. We’ll consider them in the next installment of this series.