Bottleneck Size-Dependent Changes in the Genetic Diversity and Specific Growth Rate of a Rotavirus A Strain

Abstract

RNA viruses form a dynamic distribution of mutant swarm (termed “quasispecies”) due to the accumulation of mutations in the viral genome. The genetic diversity of a viral population is affected by several factors, including a bottleneck effect. Human-to-human transmission ex-emplifies a bottleneck effect in that only part of a viral population can reach the next susceptible hosts. In the present study, the rhesus rotavirus (RRV) strain of Rotavirus A was serially passaged five times at a multiplicity of infection (MOI) of 0.1 or 0.001 in duplicate (the 1st and 2nd lineages), and three phenotypes (infectious titer, cell binding ability and specific growth rate) were used to evaluate the impact of a bottleneck effect on the RRV population. The specific growth rate values of lineages passaged under the stronger bottleneck (MOI of 0.001) were higher after five passages. The nucleotide diversity also increased, which indicated that the mutant swarms of the lineages under the stronger bottleneck effect were expanded through the serial passages. The random distribution of synonymous and non-synonymous substitutions on rotaviral genome segments indicated that almost all mutations were selectively neutral. Simple simulations revealed that the presence of minor mutants could influence the specific growth rate of a population in a mutant frequency-dependent manner. These results indicate that a stronger bottleneck effect can create more sequence spaces for minor mutants originally existing in a hidden layer of mutant swarm.IMPORTANCEIn this study, we investigated a bottleneck effect on an RRV population, which may drastically impact a viral population structure. RRV populations were serially passaged under two levels of a bottleneck effect, which exemplified a human-to-human transmission. As a result, the genetic diversity and specific growth rate of RRV populations increased under the stronger bottleneck effect, which implied that a bottleneck could create a new sequence space in a population for minor mutants originally existing in a hidden layer of a mutant swarm of the double-stranded RNA virus. The results of this study suggest that the genetic drift caused by a bottleneck in a human-to-human transmission explains the random appearance of new genetic lineages causing viral outbreaks, which can be expected by the molecular epidemiology using next generation sequencing in which the viral genetic diversity within a viral population is investigated.

Genetic diversity of murine norovirus populations less susceptible to chlorine

“…The entire serial passage experiment of MNV was performed in duplicate (rounds 1 and 2) for each population to assess the reproducibility of the responses to chlorine (Figure 1). Furthermore, as the susceptibility of the RNA virus population to disinfectants may differ, the virus population in each passage was analyzed separately for the first and second rounds (Rachmadi et al, 2018;Kadoya et al, 2022;Oishi et al, 2022).…”

“…where p is the site of polymorphism, Ni is the nucleotide difference proportion at the ith site, L is the sequence length, ki is the coverage of the sequence at the ith site, and Ai, Ci, Gi, and Ti are the sums of the four bases at the ith site (Nei and Gojobori, 1986;Kadoya et al, 2022). The nucleotide diversity in nonsynonymous and synonymous coding sites (π N and π S, respectively) was determined separately using the same formula as the nucleotide diversity.…”

“…Chlorination inactivates viruses by damaging their nucleic acids and proteins, which interfere with viral genome replication (Qiao et al, 2022). The concentration of the disinfectant, exposure time, pH, temperature, and virus type are the essential factors determining the effectiveness of the disinfection (Rachmadi et al, 2018;Lin et al, 2020;Kadoya et al, 2022;Oishi et al, 2022). Numerous studies have highlighted the variability in disinfection sensitivity among different virus types and even within specific serotypes and genotypes.…”

“…Consequently, RNA viruses can evolve rapidly and adapt to various environmental conditions. Certain genetic variations within the viral genome can cause resistance or reduce the sensitivity to disinfectants (Kadoya et al, 2022;Oishi et al, 2022). However, the genetic characteristics that contribute to alterations in susceptibility to particular disinfectants are not understood.…”

Diverged and Active Partitiviruses in Lichen

“…To date, several methods to construct (meta)genomic sequencing libraries from RNA viral genomes have been established and applied to environmental samples (Culley et al, 2006;Roossinck et al, 2010;Steward et al, 2013;Urayama et al, 2016Urayama et al, , 2018bDecker et al, 2019). Among them, fragmented and primer ligated dsRNA sequencing (FLDS) has remarkable advantages in construction of complete viral genomes (Urayama et al, 2018a;Fukasawa et al, 2020;Kadoya et al, 2020). In this study, we applied dsRNAseq and ssRNA-seq techniques to elucidate RNA virus diversity associated with a lichen.…”