Vall d'Hebron Talks by VHIR 'Viral quasispecies: concept, extensions to cells, and disease implications'

Speaker: Dr. Esteban Domingo, Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain

Abstract:
Viral quasispecies are dynamic and complex mixtures of viral genomes that replicate within infected hosts; they are termed mutant spectra, distributions, swarms or clouds. They harbor information on virus adaptability, virus-host interactions, and disease mechanisms, that is largely lost when a mutant spectrum is condensed into a consensus sequence. A well-established consequence of quasispecies dynamics is the need of administration of combinations of antiviral agents (ideally broad-spectrum) to minimize selection of treatment-escape mutants. An uncomfortable consequence is that individual pan-genomic antiviral agents or universal vaccines are unlikely to be effective, despite huge efforts in talent and money to develop them. A reason is that residue conservation differs in mutant spectra (the entities that cause pathology) and in consensus sequences (those deposited in data banks on which the design of universal reagents rests). Current evidence suggests that the implications of quasispecies dynamics apply also to SARS-CoV-2, despite having a large RNA genome that encodes a proofreading-repair activity. Mutant spectra of clonal SARS-CoV-2 populations display a 6-fold lower average number of mutations per viable genome than other RNA viruses with a shorter genome. Despite this difference, SARS-CoV-2 mutant spectra show a high complexity that increases significantly from clonal populations to clinical isolates. The complexity decreased as the COVID-19 pandemic expanded, suggesting that it may reflect not only mutational input during viral replication but also pathogenic features of the virus. While viruses remain a paradigm of biological complexity, the last decade has seen a rush of parallel concepts for cells (in normal tissues and cancer) and in macromolecules, notably prions. There are similarities and differences between viral, cellular and macromolecular quasispecies, but over all of them plans the interesting dilemma of the relative role of regulated versus stochastic processes in biology.  A new era in biomedicine has begun of awareness of the implications of complexity beyond viruses.

Host: Dr. Josep Quer, Main researcher Liver Diseases. Vall d'Hebron Research Institute (VHIR)

Online assistance: https://gencat.zoom.us/j/83072581512