Using Resurrected Ancestral Proviral Proteins to Engineer Virus Resistance

Cell Reports
Asunción DelgadoJose M Sanchez-Ruiz

Abstract

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.

Citations

Nov 22, 2019·The Biochemical Journal·Gloria Gamiz-ArcoJose M Sanchez-Ruiz
Jan 6, 2018·Evolutionary Applications·Lawrence J WeiderDagmar Frisch
Aug 2, 2019·The Journal of Biological Chemistry·Silvia NapolitanoRudi Glockshuber
Apr 6, 2021·IScience·Raquel Luzon-HidalgoJose M Sanchez-Ruiz
Jul 30, 2021·Biochimica Et Biophysica Acta. General Subjects·Monika ŠimoliūnienėLidija Truncaitė

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