Group effort from poliovirus

Group effort from poliovirus he pathogenesis of poliovirus relies on virus diversity per se, not the selection of any particular adaptive mutation, say Marco Vignuzzi, Raul Andino (UCSF, San Francisco, CA), and colleagues. Different variants may achieve different tasks in a group effort to navigate the host environment. This is how a quasispecies, or group of variants, is meant to behave, based on theory and mathematical modeling. “But really this is the first study that provides experimental evidence,” says Andino. Andino had previously used a mutagen to push viruses into evolutionary oblivion; he now uses a mutant that survives this treatment because of a less error-prone polymerase. These G64S viruses generated far fewer chemical-resistant variants and responded poorly to a challenge with this antiviral drug. But G64S was also far less potent in mice: it had to be given in a 300-fold higher dose to cause 50% lethality, and was unable to establish infection in the spinal cord and brain. Treating G64S with a chemical mutagen before inoculation restored its sequence diversity and in vivo potency. Virus reisolated from the brain did not, however, show signs of a particular variant being selected for competency to enter the spinal cord. Indeed, this isolated virus was less diverse than the original, mutagen-treated stock, and was by itself unable to reinfect the central nervous system of mice. Cooperation also occurs during coinfections, where one virus species can infect only in the presence of another. For now, Andino has few clues about how the quasispecies might be dividing up tasks in the body, but he is devising a microarray-based method to map the diversity that polio needs to conquer a host. Reference: Vignuzzi, M., et al. 2005. Nature. doi:10.1038/nature04388. T