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Recombination in Enteroviruses Is a Biphasic Replicative Process Involving the Generation of Greater-than Genome Length ‘Imprecise’ Intermediates


The rapid evolution of most positive-sense RNA viruses enables them to escape immune surveillance and adapt to new hosts. Genetic variation arises due to their error-prone RNA polymerases and by recombination of viral genomes in co-infected cells. We have developed a novel approach to analyse the poorly understood mechanism of recombination using a poliovirus model system. We characterised the initial viable recombinants and demonstrate the majority are longer than genome length due to an imprecise crossover event that duplicates part of the genome. These viruses are unfit, but rapidly lose the duplicated material and regain full fitness upon serial passage, a process we term resolution. We show this is a replicative recombination process by modifying the fidelity of the viral polymerase, or replication complex coalescence, using methods that have no influence on a previously reported, less efficient, non-replicative recombination mechanism. We conclude that recombination is a biphasic process involving separate generation and resolution events. These new insights into an important evolutionary mechanism have implications for our understanding of virus evolution through partial genome duplication, they suggest ways in which recombination might be modified and provides an approach that may be exploited to analyse recombination in other RNA viruses.


Vyšlo v časopise: Recombination in Enteroviruses Is a Biphasic Replicative Process Involving the Generation of Greater-than Genome Length ‘Imprecise’ Intermediates. PLoS Pathog 10(6): e32767. doi:10.1371/journal.ppat.1004191
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004191

Souhrn

The rapid evolution of most positive-sense RNA viruses enables them to escape immune surveillance and adapt to new hosts. Genetic variation arises due to their error-prone RNA polymerases and by recombination of viral genomes in co-infected cells. We have developed a novel approach to analyse the poorly understood mechanism of recombination using a poliovirus model system. We characterised the initial viable recombinants and demonstrate the majority are longer than genome length due to an imprecise crossover event that duplicates part of the genome. These viruses are unfit, but rapidly lose the duplicated material and regain full fitness upon serial passage, a process we term resolution. We show this is a replicative recombination process by modifying the fidelity of the viral polymerase, or replication complex coalescence, using methods that have no influence on a previously reported, less efficient, non-replicative recombination mechanism. We conclude that recombination is a biphasic process involving separate generation and resolution events. These new insights into an important evolutionary mechanism have implications for our understanding of virus evolution through partial genome duplication, they suggest ways in which recombination might be modified and provides an approach that may be exploited to analyse recombination in other RNA viruses.


Zdroje

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