Using Resurrected Ancestral Proviral Proteins to Engineer Virus Resistance

• Published in: Cell reports (Cambridge) Vol. 19; no. 6; pp. 1247 - 1256
• Main Authors: Delgado, Asunción, Arco, Rocio, Ibarra-Molero, Beatriz, Sanchez-Ruiz, Jose M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 09.05.2017; Elsevier
• Subjects: ancestral proteins; Bacteriophage T7 - pathogenicity; Bacteriophage T7 - physiology; Escherichia coli - genetics; Escherichia coli - virology; Escherichia coli Proteins - genetics; Escherichia coli Proteins - metabolism; Evolution, Molecular; Host-Pathogen Interactions; organismal fitness; Plant Immunity; Plant Proteins - genetics; Plants - virology; proviral proteins; Thioredoxins - genetics; Thioredoxins - metabolism; Virus Replication; virus resistance; ancestral proteins; organismal fitness; virus resistance; proviral proteins
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2017.04.037

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. [Display omitted] •Modern to ancestral replacement of a proviral factor prevents virus propagation•This result points to an approach to the engineering of virus resistance•This approach could potentially be applied to the engineering of plant virus resistance•Ancestral reconstruction may probe the evolution of biomolecular interactions Proviral factors are host proteins hijacked by viruses for processes essential for virus propagation. Pathogens and their hosts co-evolve. Delgado et al. show that replacing a proviral factor with a functional ancestral analog may prevent viral propagation thus pointing to an approach to the engineering of virus resistance.