Existing host range mutations constrain further emergence of RNA viruses

Abstract

RNA viruses are capable of rapid host shifting, typically due to a point mutation that confers expanded host range. As additional point mutations are necessary for further expansions, epistasis among host range mutations can potentially affect the mutational neighborhood and frequency of niche expansion. We mapped the mutational neighborhood of host range expansion using three genotypes of the dsRNA bacteriophage phi6 (wildtype and two isogenic host range mutants) on the novel host Pseudomonas syringae pv. atrofaciens (PA). Sanger sequencing of fifty PA mutant clones for each genotype and population Illumina sequencing both revealed the same high frequency mutations allowing infection of PA. Wildtype phi6 had at least nine different ways of mutating to enter the novel host, eight of which are in p3 (host attachment protein gene), and 13/50 clones had unchanged p3 genes. However, the two isogenic mutants had dramatically restricted neighborhoods: only one or two mutations, all in p3. Deep sequencing revealed that wildtype clones without mutations in p3 likely had changes in p12 (morphogenic protein), a region that was not polymorphic for the two isogenic host range mutants. Sanger sequencing confirmed that 10/13 of the wildtype phi6 clones had nonsynonymous mutations in p12 and two others had point mutations in p9 and p5 -none of these genes had previously been associated with host range expansion in phi6. We demonstrate, for the first time, epistatic constraint in an RNA virus due to host range mutations themselves, which has implications for models of serial host range expansion. ImportanceRNA viruses mutate rapidly and frequently expand their host ranges to infect novel hosts, leading to serial host shifts. Using an RNA bacteriophage model system (Pseudomonas phage phi6), we studied the impact of pre-existing host range mutations on another host range expansion. Results from both clonal Sanger and Illumina sequencing show extant host range mutations dramatically narrow the neighborhood of potential host range mutations compared to wildtype phi6. This research suggests that serial host shifting viruses may follow a small number of molecular paths to enter additional novel hosts. We also identified . CC-BY-NC 4.0

Variation Profile of the Orthotospovirus Genome

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Gauging genetic diversity of generalists: A test of genetic and ecological generalism with RNA virus experimental evolution

“…Raw reads were trimmed and filtered with cutadapt 1.12 (Q score cutoff: 30, minimum length cutoff: 75 bp, adapters and terminal Ns of reads removed) (Martin 2011). The reference genomes for the S and G genotypes were obtained from Day 0 Illumina sequencing results, and these full-length sequences were identical to the sequences obtained through Sanger sequencing of the same stocks (Zhao et al. 2019).…”

Variable routes to genomic and host adaptation among coronaviruses

“…Host shifts and subsequent adaptation to the new host are particularly important in viral evolution (Forni et al., 2016; Mollentze et al., 2014) and in the emergence of viral infectious diseases in humans (Longdon et al., 2014). The generally small genome sizes and high mutation rates exhibited by RNA viruses make viral host‐switching events excellent models for investigating the genomics of adaptation (Duffy et al., 2007; Forni et al., 2016; Zhao et al., 2019). These properties of RNA viruses also quickly lead to the accretion of significant genetic variation (Drummond et al., 2003).…”

“…Viral transfer between phylogenetically proximate hosts (i.e. between mammals) is thus expected to be associated with a shallower valley between fitness peaks in the fitness landscape (Gavrilets, 2004), with fewer mutations required for colonization and adaptation to the novel host (Zhao et al., 2019). In contrast, viral transfer between phylogenetically distant hosts is expected to be associated with a deep fitness valley requiring more extensive host‐specific adaptation to facilitate colonization of the new host (Olival et al., 2017).…”