Paper Review: Dual Host-Virus Arms Races Shape an Essential Housekeeping Protein

Demogines, A., Abraham, J., Choe, H., Farzan, M., & Sawyer, S. (2013). Dual Host-Virus Arms Races Shape an Essential Housekeeping Protein PLoS Biology, 11 (5) DOI: 10.1371/journal.pbio.1001571

This paper is not really related to my research, but I always enjoy a good cell biology story. My review is thus mostly a retelling of what I think were the highlights of the story.

In wild rodent populations, the retrovirus MMTV and New World arenaviruses both exploit Transferrin Receptor 1 (TfR1) to enter the cells of their hosts. Here we show that the physical interactions between these viruses and TfR1 have triggered evolutionary arms race dynamics that have directly modified the sequence of TfR1 and at least one of the viruses involved.

What is most interesting is that TfR1 is a housekeeping gene involved in iron uptake, which is essential for survival. Thus, it is probably highly constrained in its defensive evolution as even a small loss of function can be deleterious for the host.

The authors looked at the specific residues which seem to mutate rapidly in rodent species and they map to known virus/protein contact regions (which are known from X-ray crystallography).

Interestingly, the same evolutionary patterns are visible in rodent species for which no known virus use this entry point. However (and this is cool) we can find viral fossils in the genome of these rodents (i.e., we can parts of the viral sequence in the genome, which indicate that somewhere in the evolutionary past of these animals, a retrovirus integrated into the genome).

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This process also explains why some viruses infect some species and not others: divergent evolution of the virus itself to catch up with the defensive evolution of different hosts makes them unable to infect across species. Thus, whenever the host mutates, it forces the virus gene to make an awkward choice: does it want to chase the new host surface and specialize to this species or let this species go as a possible target?

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