Using Resurrected Ancestral Proviral Proteins to Engineer Virus Resistance

Publication date: 9 May 2017
Source:Cell Reports, Volume 19, Issue 6
Author(s): Asunción Delgado, Rocio Arco, Beatriz Ibarra-Molero, Jose M. Sanchez-Ruiz
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.

Graphical abstract

Teaser

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.


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