Unfolding Evolutionary Modular Proteomics, Knowledge-driven Molecular Epidemiology and HTS-based Phylogenomic Diversity of Closteroviruses Associated with The Little Cherry Disease

The ongoing Little cherry Disease (LChD) global pandemic has piqued public interest in the properties, evolution, and emergence of its associated plant viruses little cherry virus 1 (LChV-1) and little cherry virus 2 (LChV-2). There is a realistic expectation that global efforts in LChD management combined to new HTS-based diagnostic platforms will bring LChV newly triggered outbreaks under reasonable control. Nonetheless, uncertainties remain about latent infection in long-term association that both viruses can establish with Prunus germplasms or wild species and new potential vectors. Although the epidemiological trajectories are difficult to predict, the current conditions and biological variables that influence epidemiology can be proactively anticipated. Persistence of both endemic plant viruses of sweet and sour cherry, perhaps with seasonal epidemicity, may be fueled by reservoirs of new susceptible cultivated Prunus cultivars or rootstocks and post-infection waning resistance and genetic variability through evolutionary drift that hampers host immune protection. Here, I addressed relevant field observations from surveyed LChD outbreaks and explored patterns of LChV phylogenomic evolution as it adapts mainly during its graft-transmission through diverse horticultural eco-systems. Furthermore, the lack of reliable diagnostics or adequate response often enables the surge of new LChV hotspots. In this research, while proposing new diagnostic solutions, key pieces of data have been unveiled in order to draw evidence-based regulatory plant health decisions.
From an evolutionary vantage, hypotheses on phylogenomic origin of viruses members of the family Closteroviridae remain unclear because of their diverse and mosaic evolutionary functional proteomic makeup (we coined for the first time here The Modulome). In the second frame of this thesis, I take full advantage of the abundant protein structural and functional data to explore the Modulome of little cherry viruses in the context of the global plant proteome. The discovery of modularity patterns and their wide-spread distribution further shifted our standard paradigms. Using cutting-edge bioinformatics, our comparative proteome-wide data-driven analyses were extended to the study of all detected conformational fold families and their assigned functions confirming their modulation role in the co-evolutionary processes governing vector-based transmission modes fostered by modular innovation. In light of this structural complexity unique insights prompted a critical redefinition and reclassification of plant viruses. Based on primordial evolution of structural domains in the genomes of Closteroviridae, I made robust inference on the ancestry of viral exaptations traced from their co-evolving hosts and draw novel timescaled hypothetical macroevolutionary scenari based on sheaves of novel robust evidence. From more innovative perspectives, the study of intrinsic disordered regions in the proteins (IDR/Ps) of plant viruses remain untapped. To fill this gap, we used the most widely reliable artificial intelligence-based algorithms to predict IDP signatures in viruses of the Closteroviridae taxon, including LChV-1 and LChV-2 benchmarked against the global Modulome.For the first time, I unraveled the IDRs occurrence and abundance, where they operate important modulatory roles and supplement the multifunctionality of diverse viral structural interacting modules, in particular those involved in vector-based transmission. Our Disordome-wide analysis also uniquely established that conserved IDRs signatures adorned with protein molecular recognition features (MoRFs) in plant viruses and vector modules are likely to promote multifunctionality by encoding more non-optimal codon biases. Collectively, these forays offer novel outlooks on the structural evolution of viral IDP as multifaceted evolutionary forces that shape the global plant virome and predominantly govern viral functional adaptability during interactions with phylogenomically divergent hosts.
In conclusion, during this research, the deployed efforts shed new light into the ancestral origins, epidemiology and evolution of closteroviruses and elucidated determinants that resist the widespread acceptance of new views and insights. I proposed a new definition of the little cherry disease that is not restricted to the oversimplified presence or absence LChV-1and/or -2 or symptomatic features. I also discuss general views for how plant viruses likely enduringly modulate their interactions according to the fine-tuned evolutionary proteomic signatures, and unearth the conceptual biases that may limit our understanding of virus evolution and classification. With the prism of functional modular evolution, I discuss how these fundamental aspects have surprisingly remained disputed despite being increasingly used within the reach of scientific thinking. Lastly, I introspect few philosophical concepts evolutionary structural virology, symbiopoeisis and viral disease and their impact on the way we might predict future LChD outbreaks.