Abstract
RNA genomes are vulnerable to corruption by a range of activities, including inaccurate replication by the error-prone replicase, damage from environmental factors, and attack by nucleases and other RNA-modifying enzymes that comprise the cellular intrinsic or innate immune response. Damage to coding regions and loss of critical cis-acting signals inevitably impair genome fitness; as a consequence, RNA viruses have evolved a variety of mechanisms to protect their genome integrity. These include mechanisms to promote replicase fidelity, recombination activities that allow exchange of sequences between different RNA templates, and mechanisms to repair the genome termini. In this article, we review examples of these processes from a range of RNA viruses to showcase the diverse approaches that viruses have evolved to maintain their genome sequence integrity, focusing first on mechanisms that viruses use to protect their entire genome, and then concentrating on mechanisms that allow protection of the genome termini, which are especially vulnerable. In addition, we discuss examples in which it might be beneficial for a virus to 'lose' its genomic termini and reduce its replication efficiency.
Highlights
RNA genomes are vulnerable to corruption by a range of activities, including inaccurate replication by the error-prone replicase, damage from environmental factors, and attack by nucleases and other RNA-modifying enzymes that comprise the cellular intrinsic or innate immune response
There is a significant range in RNA virus genome length, with the filoviruses and some paramyxoviruses having genome lengths of 18–19 kb, more than 7-fold longer than the genomes of the smallest RNA viruses, and the coronaviruses being even larger, with maximum genome sizes between 27 and 32 kb
Fearns nsp14 protein are more error-prone than wild-type virus by a factor of at least 15-fold (Eckerle et al, 2007). These data suggest that nsp14 acts as an exonuclease to remove and repair misincorporated nucleotides, helping to maintain the sequence integrity of the large coronavirus RNA genomes
Summary
RNA genomes are vulnerable to corruption by a range of activities, including inaccurate replication by the error-prone replicase, damage from environmental factors, and attack by nucleases and other RNA-modifying enzymes that comprise the cellular intrinsic or innate immune response. Damage to coding regions and loss of critical cis-acting signals inevitably impair genome fitness; as a consequence, RNA viruses have evolved a variety of mechanisms to protect their genome integrity. These include mechanisms to promote replicase fidelity, recombination activities that allow exchange of sequences between different RNA templates, and mechanisms to repair the genome termini. We review examples of these processes from a range of RNA viruses to showcase the diverse approaches that viruses have evolved to maintain their genome sequence integrity, focusing first on mechanisms that viruses use to protect their entire genome, and concentrating on mechanisms that allow protection of the genome termini, which are especially vulnerable. We discuss examples in which it might be beneficial for a virus to ‘lose’ its genomic termini and reduce its replication efficiency
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