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Disorder is adaptive for viruses

Certain plant viruses encode "disordered" proteins, whose structural flexibility can more easily accommodate mutations. These proteins may increase virus adaptability and, in particular, allow viruses to evade genetically enhanced crop resistance. This advantage has been experimentally demonstrated for the first time by infecting resistant pepper plants with high-disorder Potato virus Y mutants.

Pepper plants that are vulnerable and resistant to Potato virus Y (on the left and right, respectively). © INRA, PALLOIX Alain
Updated on 12/06/2017
Published on 11/08/2017

Flexible proteins increase virus adaptability

Potyviruses cause major damage to agricultural crops. They belong to a special subgroup of RNA viruses that can encode proteins with intrinsically disordered regions (IDRs). Compared to structured regions, IDRs are subject to fewer conformational constraints. Therefore, amino acid substitutions that occur within IDRs have less of an effect on protein function. Consequently, the mutations underlying such substitutions are more easily accommodated, and some may ultimately prove to be adaptive, allowing the virus to overcome host resistance. This flexibility may thus significantly enhance the overall adaptive potential of potyviruses.

We can use an architectural analogy to illustrate this concept. In red is a pagoda held aloft by a single column. It is equivalent to a compact, structured protein. In green is a beach house perched upon stilts. It is equivalent to a flexible protein containing IDRs. Mutations are like the strokes of an axe. In the case of the pagoda, any axe strokes will be focused on the single column, which is the sole source for the building’s stability. When the column gives way, the entire structure will give way. In contrast, in the case of the beach house, any axe strokes will be spread across the many stilts, leading to a more gradual loss of structural stability. Taken from Charon 2015. Contribution of protein intrinsic disorder to functions involved in the viral cycle and adaptive evolution of RNA viruses: study applied to the potyvirus genus. PhD thesis, University of Bordeaux. © INRA, INRA, Thierry Michon/UMR BFP
We can use an architectural analogy to illustrate this concept. In red is a pagoda held aloft by a single column. It is equivalent to a compact, structured protein. In green is a beach house perched upon stilts. It is equivalent to a flexible protein containing IDRs. Mutations are like the strokes of an axe. In the case of the pagoda, any axe strokes will be focused on the single column, which is the sole source for the building’s stability. When the column gives way, the entire structure will give way. In contrast, in the case of the beach house, any axe strokes will be spread across the many stilts, leading to a more gradual loss of structural stability. Taken from Charon 2015. Contribution of protein intrinsic disorder to functions involved in the viral cycle and adaptive evolution of RNA viruses: study applied to the potyvirus genus. PhD thesis, University of Bordeaux © INRA, INRA, Thierry Michon/UMR BFP

First experimental confirmation that flexible proteins are advantageous

To test the hypothesis that IDR-bearing proteins enhance virus adaptability, INRA researchers created three mutants of Potato virus Y1. The mutants varied in the degree of disorder2 of their viral genome-linked (VPg) protein, which plays a key role in potyvirus adaptation3. Compared to the wild type, one mutant displayed less disorder in its VPg protein, while the other two mutants displayed more disorder. Then, genetically resistant pepper plants (Capsicum annuum) were infected with the three mutants and the wild type.

Compared to the wild type, the two more-disordered mutants were significantly better at overcoming host resistance, leading to symptomatic infection in the plants; the less-disordered mutant was incapable of causing infection. After 30 days, the two more-disordered mutants had successfully caused infection in 60% and 95% of the plants, respectively; in the case of the wild type, this number was just 40%.

These results strongly support the idea that IDR-bearing proteins provide an adaptive advantage to RNA viruses.

The ability to overcome host resistance was correlated with the degree of disorder in the VPg protein. © INRA, INRA, Thierry Michon/UMR BFP
The ability to overcome host resistance was correlated with the degree of disorder in the VPg protein © INRA, INRA, Thierry Michon/UMR BFP

Helpful information for fighting viruses

This innovative study has shed light on a novel adaptive mechanism. It has also added to our understanding of plant-pathogen interactions and disease outbreaks.

Its results will also inform on how to improve our control of viral diseases. At present, the design of antiviral products and the creation of genetically resistant plants are the two main approaches to control viral diseases in animals and plants respectively. This study suggests that these conventional strategies are inappropriate for RNA viruses that encode IDR-bearing proteins, since owing to their adaptive abilities, viral IDRs could constitute poor targets of both drugs and host genetic resistance.

1 PVY; Potyvirus genus
2 To create the mutants, mutations were introduced so as to induce certain post-translational amino acid substitutions that enhanced protein disorder without affecting protein function.
3 The viral genome-linked protein (VPg) has numerous functions. In particular, it is involved in the replication of the virus genome.

reference

Charon J, Barra A, Walter J, Millot P, Hébrard E, Moury B, Michon T. 2017. First experimental assessment of protein intrinsic disorder involvement in an RNA virus natural adaptive process. Mol. Biol. Evol. https://doi.org/10.1093/molbev/msx249