Comparative and phylogenetic analysis of CHIKV genomes links lineage-associated single-nucleotide variants to changes in conserved RNA structures.
Published as Dynamic Molecular Epidemiology Reveals Lineage-Associated Single-Nucleotide Variants That Alter RNA Structure in Chikungunya Virus, Genes 2021.
Chikungunya virus is an Alphavirus with millions of human infections per year. Outbreaks have been described since the 1950s for three lineages, i.e. West African, East Central South African and Asian Urban, and strains carried into the Americas have since formed further monophyletic groups that were again named after the region where they were first seen. This paper assembles more than 900 public CHIKV genomes into a phylodynamic data set and publishes it as an interactive Nextstrain build, CHIKVnext, so that the spread can be followed in space and time instead of in a static tree.
The second half of the work connects that phylogeny with RNA structure prediction. Divergence within a lineage is low, in part because the younger lineages were sampled over a short period and in a limited area, while divergence between lineages is considerable, with the West African lineage furthest from the rest. Against that background, single nucleotide variants that occur in one lineage and not in the others become visible.
The structural question is what such a variant does to the fold around it. For more than a dozen locally stable elements the prediction changes with a single nucleotide: the structure ensemble shifts, and different lineages are predicted to form different structures at the same position of the genome. These are predictions from sequence data, so they say where to look rather than what the virus does.
Two consequences follow for practice: naming lineages after the region of first detection stops being useful once strains move between continents, so a nomenclature independent of geography would describe the diversity better. And single substitutions can matter for the phenotype, the adaptive E1 A226V mutation being the known example, which is an argument for sequencing at the time a virus is introduced rather than during an outbreak.
Chikungunya virus (CHIKV) is an emerging Alphavirus which causes millions of human infections every year. Outbreaks have been reported in Africa and Asia since the early 1950s, from three CHIKV lineages: West African, East Central South African, and Asian Urban. As new outbreaks occurred in the Americas, individual strains from the known lineages have evolved, creating new monophyletic groups that generated novel geographic-based lineages. Building on a recently updated phylogeny of CHIKV, we report here the availability of an interactive CHIKV phylodynamics dataset, which is based on more than 900 publicly available CHIKV genomes. We provide an interactive view of CHIKV molecular epidemiology built on Nextstrain, a web-based visualization framework for real-time tracking of pathogen evolution. CHIKV molecular epidemiology reveals single nucleotide variants that change the stability and fold of locally stable RNA structures. We propose alternative RNA structure formation in different CHIKV lineages by predicting more than a dozen RNA elements that are subject to perturbation of the structure ensemble upon variation of a single nucleotide.
Dynamic Molecular Epidemiology Reveals Lineage-Associated Single-Nucleotide Variants That Alter RNA Structure in Chikungunya Virus
Thomas Spicher, Markus Delitz, Adriano de Bernardi Schneider, Michael T. Wolfinger
Genes 12 (2):239 (2021) | doi:10.3390/genes12020239 | PDF | Figures
Updated Phylogeny of Chikungunya Virus Suggests Lineage-Specific RNA Architecture
Adriano de Bernardi Schneider, Roman Ochsenreiter, Reilly Hostager, Ivo L. Hofacker, Daniel Janies, Michael T. Wolfinger
Viruses 11:798 (2019) | doi:10.3390/v11090798 | PDF | Figures