Viruses use specific host receptors to infect cells, and this frequently triggers an evolutionary 'arms race', with the host mutating receptors and the virus playing 'catch-up'. In PLOS Biology, Sawyer et al. investigate how the host counters viruses that use highly conserved host receptors for entry. The transferrin receptor Tfr1 is used by certain viruses for entry into host cells, but because Tfr1 is critical for cell survival, it does not tolerate mutation well. By examining the structures and sequences of Tfr1 from different rodent species, the authors find that the entire receptor is highly conserved except for a few residues that undergo strong positive selection. Those sequences overlap the interaction surfaces of arenaviruses and mouse mammary tumor viruses that use Tfr1 for entry and thereby impose strict barriers on infection. These findings offer insight into how the host can mutate critical housekeeping genes to impede the entry of viruses without affecting essential physiological functions.

PLOS Biol. (28 May 2013) doi:10.1371/journal.pbio.1001571