Effects of multiple sources of genetic drift on pathogen variation within hosts

Abstract

1Changes in pathogen genetic variation within hosts alter the severity and spread of infectious 2 diseases, with important implications for clinical disease and public health. Genetic drift 3 may play a strong role in shaping pathogen variation, but analyses of drift in pathogens have 4 oversimplified pathogen population dynamics, either by considering dynamics only at a single 5 scale (within hosts, between hosts), or by making drastic simplifying assumptions (host immune 6 systems can be ignored, transmission bottlenecks are complete). Moreover, previous studies 7 used genetic data to infer the strength of genetic drift, whereas we test whether the genetic 8 drift imposed by pathogen population processes can be used to explain genetic data. We first 9 constructed and parameterized a mathematical model of gypsy moth baculovirus dynamics that 10 allows genetic drift to act within and between hosts. We then quantified the genome-wide 11 diversity of baculovirus populations within each of 143 field-collected gypsy moth larvae 12 using Illumina sequencing. Finally, we determined whether the genetic drift imposed by 13 host-pathogen population dynamics in our model explains the levels of pathogen diversity in 14 our data. We found that when the model allows drift to act at multiple scales, including within 15 hosts, between hosts, and between years, it can accurately reproduce the data, but when the

Population bottlenecks in multicomponent viruses: first forays into the uncharted territory of genome-formula drift

“…Many different laboratory studies have shown that population bottlenecks are common at different steps of the viral life cycle and that they occur for a wide range of viruses [27,28]. Recent studies have highlighted that population bottlenecks also occur in vertical transmission [38], and that population bottlenecks are common in natural virus populations [39]. Although severe bottlenecks-in the order of units-are common in the current literature, it is important to note that bottleneck estimates are available for a limited number of viruses [27,28,40].…”

Generation of Variability in Chrysodeixis includens Nucleopolyhedrovirus (ChinNPV): The Role of a Single Variant

“…This may be explained by a founder effect, in which a few founder genomes undergo changes in the early stages of infection which are then transmitted and amplified in other cells via the BV progeny and become the dominant variant in the majority of OB progeny collected from virus-killed insects. This effect relies on a combination of (i) the paucity of founder virus genomes in insects that consume small quantities of inoculum, as the infection of midgut cells represents an important bottleneck to the transmission of diversity [28,29], (ii) instability in the replication of these genomes early in infection and (iii) stochastic events generated by host genotype or immune condition that determine variant survival. Such effects are likely to be most evident when the founder virus population size is small [29,30].…”

“…This effect relies on a combination of (i) the paucity of founder virus genomes in insects that consume small quantities of inoculum, as the infection of midgut cells represents an important bottleneck to the transmission of diversity [28,29], (ii) instability in the replication of these genomes early in infection and (iii) stochastic events generated by host genotype or immune condition that determine variant survival. Such effects are likely to be most evident when the founder virus population size is small [29,30]. Intuitively, we would predict the influence of founder effects on variant diversity to be potentiated when variants also differ in their rate of replication.…”

“…This is usually observed in wild-type baculoviruses where the most abundant variant is often the one with the highest fitness in a given environment at a given moment [37,38]. Virus epizootics, however, involve selection during between-host transmission followed by within-host selection for a different set of traits [29]. Nevertheless, according to our previous observations [17], the ChinNPV-K genotype was not the most pathogenic variant i.e., the variant that produced the highest prevalence of mortality in inoculated insects.…”

Peer Review #1 of "Linked within-host and between-host models and data for infectious diseases: a systematic review (v0.1)"

“…However, one included paper did not explicitly fit data. Instead Kennedy and Dwyer (2018) constructed sophisticated linked within and between host models for baculovirus in gypsy moths and then the authors compared the predictions of the calibrated model to newly obtained experimental data in a validation step. Even among the relatively small sample of papers that included data at all in these multi-scale models, most did not use it for more than one scale of their model (Fig.…”