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.
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 disorder2of 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.
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.
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. DOI : doi.org/10.1093/molbev/msx249