Dual Host-Virus Arms Races Shape an Essential Housekeeping Protein

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Dual Host-Virus Arms Races Shape an Essential Housekeeping Protein

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Title: Dual Host-Virus Arms Races Shape an Essential Housekeeping Protein
Author: Demogines, Ann; Abraham, Jonathan; Choe, Hyeryun; Farzan, Michael; Sawyer, Sara L.

Note: Order does not necessarily reflect citation order of authors.

Citation: Demogines, Ann, Jonathan Abraham, Hyeryun Choe, Michael Farzan, and Sara L. Sawyer. 2013. Dual host-virus arms races shape an essential housekeeping protein. PLoS Biology 11(5): e1001571.
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Abstract: Transferrin Receptor (TfR1) is the cell-surface receptor that regulates iron uptake into cells, a process that is fundamental to life. However, TfR1 also facilitates the cellular entry of multiple mammalian viruses. We use evolutionary and functional analyses of TfR1 in the rodent clade, where two families of viruses bind this receptor, to mechanistically dissect how essential housekeeping genes like TFR1 successfully balance the opposing selective pressures exerted by host and virus. We find that while the sequence of rodent TfR1 is generally conserved, a small set of TfR1 residue positions has evolved rapidly over the speciation of rodents. Remarkably, all of these residues correspond to the two virus binding surfaces of TfR1. We show that naturally occurring mutations at these positions block virus entry while simultaneously preserving iron-uptake functionalities, both in rodent and human TfR1. Thus, by constantly replacing the amino acids encoded at just a few residue positions, TFR1 divorces adaptation to ever-changing viruses from preservation of key cellular functions. These dynamics have driven genetic divergence at the TFR1 locus that now enforces species-specific barriers to virus transmission, limiting both the cross-species and zoonotic transmission of these viruses.
Published Version: doi:10.1371/journal.pbio.1001571
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3665890/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:11357491
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