Ab selection can occur either in the transmitting host or the recipient host. In the presence of neutralizing Abs, viruses with mutations that enable escape from neutralization are rapidly selected, resulting in antigenic drift. This results in the steady accumulation of mutants as a virus circulates. Nearly every virus generated in a host (depicted as a metaphorical bottle) possesses at least one point mutation. Transmission of a very limited number of viruses between hosts (bottlenecking, 5 different mutants in the figures) results in the random selection of mutants that compete in the new host (generating a hierarchy as shown, with the blue virus becoming extinct with the purple virus at the top), all the while generating a new repertoire of mutants that are bottlenecked in transmitting to the next host.
Mutations that do not compromise viral replication and transmission are randomly propagated and “fixed” in a virus population when a small number of virions (sometimes just one) transmits the infection to a new host. Genetic drift is the inevitable consequence of high viral mutation rates. It is important to distinguish this “genetic drift” from antigenic drift ( Figure 1 see Box 1įor terms defined). Such continuously generated robust genetic diversity allows viruses to evolve rapidly under host immune pressure. For the many viruses with high mutation rates, this swarm includes viruses with mutations at each position in the genome and even viruses with all possible nucleotides at any two positions. Infected humans can produce 10 12 virions-infectious viral particles-during a respiratory virus infection. Viral genetic variation is further enhanced by codon deletions and/or insertions and recombination between viral genomes, a feature common in coronaviruses (CoVs), and occasionally between viral and host genomes. This typically results in each progeny virus having at least one point mutation per genome. Viral DNA or RNA polymerases exchange accuracy for efficiency, generating nucleotide substitutions at rates upward of 1 substitution per 5,000 copied nucleotides (mutation rate of 2 × 10 −4 per base pair by comparison, the error rate in replicating the human genome is 6,000 times lower). Viral genomes encode relatively simple proteomes that are still sufficient to hijack host cell biosynthetic machinery and produce up to a million offspring viruses from a single infectious cycle in a single day. Viruses have small genomes that are quickly replicated upon viral proliferation, facilitating rapid adaptive evolution. The estimated 10 33 viruses that constitute the virome are earth’s most abundant self-replicating entity.
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