A Careful Escape

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Science  14 Jun 2013:
Vol. 340, Issue 6138, pp. 1267
DOI: 10.1126/science.340.6138.1267-c

Viruses gain entry to host cells through binding to specific receptors, which subsequently mutate to block virus binding. This can be problematic, however, because many viral receptors perform essential functions for their hosts. One such example is transferrin receptor 1, which regulates iron uptake by host cells. How are such mutations selected so as to not disrupt the essential function of the receptor? Demogines et al. now show how a small number of mutations in transferrin receptor 1 can alter viral host specificity. Analysis of the ratio of synonymous to nonsynonymous DNA mutations in the rodent transferrin receptor identified a handful of residues that were under positive selection. These residues corresponded to the region of the receptor that interacts with the virus rather than those residues necessary for iron uptake. A search for human single-nucleotide polymorphisms identified transferrin receptor variants that reduced viral uptake in cultured human cells but maintained iron regulation. These results demonstrate that in the constant arms race between viruses and the cells they infect, positive selection of residues involved in viral entry can be divorced from regions of the receptor that are essential for host function.

PLoS Biol. 11, e1001571 (2013).

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