Using Resurrected Ancestral Proviral Proteins to Engineer Virus Resistance
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Ancestral proteinsVirus resistanceProviral proteinsOrganismal fitness
Delgado, A.; et al. Using Resurrected Ancestral Proviral Proteins to Engineer Virus Resistance. Cell Reports, 19: 1247-1256 (2017). [http://hdl.handle.net/10481/46292]
SponsorshipThis work was supported by grants BIO2012-34937, CSD2009-00088, and BIO2015-66426-R (J.M.S.-R.) from MINECO/FEFER and grant P09-CVI-5073 (B.I.-M.) from the “Junta de Andalucía” and Feder Funds.
Proviral factors are host proteins hijacked by viruses for processes essential for virus propagation such as cellular entry and replication. Pathogens and their hosts co-evolve. It follows that replacing a proviral factor with a functional ancestral form of the same protein could prevent viral propagation without fatally compromising organismal fitness. Here, we provide proof of concept of this notion. Thioredoxins serve as general oxidoreductases in all known cells. We report that several laboratory resurrections of Precambrian thioredoxins display substantial levels of functionality within Escherichia coli. Unlike E. coli thioredoxin, however, these ancestral thioredoxins are not efficiently recruited by the bacteriophage T7 for its replisome and therefore prevent phage propagation in E. coli. These results suggest an approach to the engineering of virus resistance. Diseases caused by viruses may have a devastating effect in agriculture. We discuss how the suggested approach could be applied to the engineering of plant virus resistance.