Wednesday, May 10, 2017

Reconstruction of ancestral thioredoxins could be a novel source of plant virus resistance

Non-enveloped, head-tail structure. Head is about 60 nm in diameter. The tail is non-contractile, has 6 short subterminal fibers. The capsid is icosahedral with a T=7 symmetry. Via ViralZone.
Viruses and their hosts are engaged in a constant evolutionary battle with one developing defenses and the other subverting those defenses. Along the way, it is thought that some of these adaptations in the virus are lost as the host mutates targets. But this isn't known for sure. To answer this question, scientists reconstructed an ancient ancestral thioredoxin, a small protein that is vital in many organisms, using bioinformatics software for E. coli. Thioredoxins are also a protein that many viruses interact with and will suppress as thioredoxins are involved in defense against viruses. The researchers found that not only was the reconstructed thioredoxin functional in E. coli (if thioredoxin is not functional, it is lethal), but the cells were highly resistant to infection by the T7 bacteriophage.

This work was proof of the concept for the researchers. Their end goal is to use this technique with crop plants to develop novel sources of plant virus resistance by using an ancestral thioredoxin in place of the modern version. They outline the following steps that would need to be taken:
"(1) A known proviral factor in a plant is selected as a target. Obviously, this factor would be a protein that is hijacked (or suspected to be hijacked) by the virus or viruses for which we wish to engineer resistance.
(2) The known sequence of this protein is used as a search query in a sequence database.
(3) The sequences recovered from the search (belonging to homologs of the targeted protein) are aligned and the alignment is used as input for ancestral sequence reconstruction.
(4) The “modern” proviral factor is replaced by a reconstructed ancestral counterpart. Actually, ancestral sequences for many phylogenetic nodes can be derived from a single alignment of modern proteins and, therefore, the replacement could be actually performed with many different ancestral proteins leading to many engineered plant variants.
(5) The engineered plant variants are screened for fitness under conditions of interest (normal growth conditions, for instance) and for virus resistance." The use of reconstructed ancestral genes is an newer area of research and it could be a novel source of diversity for plant breeding efforts. With CRISPR-Cas systems, it would be relatively straightforward to "swap" out the modern version of a protein for a reconstructed ancestral version. The researchers are still developing this technique for plant virus resistance, but it holds promise and I look forward to the results.

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