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Viral genetics

Interference tactics

Nature Reviews Genetics volume 6, page 593 (2005)Cite this article

All viruses mutate at high rates, but those with a single-stranded RNA genome, such as poliovirus, top them all and are therefore most adept at evolving resistance to conventional drugs. Scott Crowder and Karla Kirkegaard tried an alternative tactic, which involved identifying mutant lines of poliovirus that could interfere in a dominant–negative way with the growth of wild-type particles. Using reverse engineering, they produced a series of poliovirus genomes and then selected those that generated non-viable (that is, growth-defective) particles. Next, they co-transfected mutant and wild-type viruses into cells and investigated whether the yield of wild-type viruses had been affected.

The dominant mutations, which fell into four classes, were very effective. For example, dominant mutations in several capsid proteins inhibited the growth of wild-type viruses by 93%, on average, in just one round of co-infection. But how successful would such a virus-busting strategy be? One test shows that the predicted benefits translate well into practice: a dominant drug-sensitive virus was able to cut the yield of a co-transfected drug-resistant virus down to 3–7% of its normal titre — presumably because the dominant capsid protein destabilized the multi-subunit coat of the resistant virus.

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ORIGINAL RESEARCH PAPER

  1. Crowder, S. & Kirkegaard, K. Trans-dominant inhibition of RNA viral replication can slow growth of drug-resistant viruses. Nature Genet. 19 June 2005 (10.1038/ng1583)

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Authors
  1. Tanita Casci
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Casci, T. Interference tactics. Nat Rev Genet 6, 593 (2005). https://doi.org/10.1038/nrg1671

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