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Cell Rep. 2017 May 9;19(6):1247-1256. doi: 10.1016/j.celrep.2017.04.037.

Using Resurrected Ancestral Proviral Proteins to Engineer Virus Resistance.

Author information

1
Facultad de Ciencias, Departamento de Quimica Fisica, Universidad de Granada, 18071 Granada, Spain.
2
Facultad de Ciencias, Departamento de Quimica Fisica, Universidad de Granada, 18071 Granada, Spain. Electronic address: sanchezr@ugr.es.

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.

KEYWORDS:

ancestral proteins; organismal fitness; proviral proteins; virus resistance

PMID:
28494872
DOI:
10.1016/j.celrep.2017.04.037
[Indexed for MEDLINE]
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