Stochastic processes constrain the within and between host evolution of influenza virus
- University of Michigan, United States
Figures
Figure 1 with 4 supplements
Within-host diversity of IAV populations.
(A) Boxplots (median, 25th and 75th percentiles, whiskers extend to most extreme point within median ±1.5 x IQR) of the number of viral genomes per microliter transport media stratified by day post …
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Figure 1—source data 1
Titers and day of sampling for all samples processed from the cohort.
- https://doi.org/10.7554/eLife.35962.008
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Figure 1—source data 2
The number of iSNV and day of sampling for samples that qualified for iSNV identification.
- https://doi.org/10.7554/eLife.35962.009
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Figure 1—source data 3
The number of iSNV and vaccination status for samples that qualified for iSNV identification.
- https://doi.org/10.7554/eLife.35962.010
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Figure 1—source data 4
Location and frequency of iSNV identified in each individual.
(The highest quality sample was used when two where available).
- https://doi.org/10.7554/eLife.35962.011
Figure 1—figure supplement 1
Sequence coverage for all samples.
For each sample, the sliding window mean coverage was calculated using a window size of 200 and a step of 100. The distributions of these means are plotted as box plots (median, 25th and 75th …
Figure 1—figure supplement 2
Approximate maximum likelihood trees of the concatenated coding sequences for high quality H1N1 samples.
The branches are colored by season; the tip identifiers are colored by household. Arrows with numbers indicate consensus and putative minor haplotypes for samples with greater than 10 iSNV. Trees …
Figure 1—figure supplement 3
Approximate maximum likelihood trees of the concatenated coding sequences for high quality H3N2 samples.
The branches are colored by season; the tip identifiers are colored by household. Arrows with numbers indicate consensus and putative minor haplotypes for samples with greater than 10 iSNV. Trees …
Figure 1—figure supplement 4
The effect of titer on the number of iSNV identified.
(A) The number of iSNV identified in an isolate (y-axis) plotted against the titer (x-axis, genomes/μl transport media).
Figure 2 with 1 supplement
Within-host dynamics of IAV.
(A) Histogram of within-host iSNV frequency in 249 high quality samples. Bin width is 0.05 beginning at 0.02. As in Figure 1, mutations were classified as nonsynonymous (blue) if they were …
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Figure 2—source data 1
The frequency and class (nonsynonymous/synonymous) of identified iSNV.
- https://doi.org/10.7554/eLife.35962.014
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Figure 2—source data 2
Meta data for nonsynonymous iSNV found in HA.
- https://doi.org/10.7554/eLife.35962.015
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Figure 2—source data 3
Frequency and meta data for antigenic iSNV that were also identified at the global level.
- https://doi.org/10.7554/eLife.35962.016
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Figure 2—source data 4
Sampling day for within-host sample pairs.
- https://doi.org/10.7554/eLife.35962.017
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Figure 2—source data 5
Frequencies of mutations identified in longitudinal sample pairs.
- https://doi.org/10.7554/eLife.35962.018
Figure 2—figure supplement 1
(A) Reproducibility of iSNV identification for paired samples acquired on the same day.
The x-axis represents iSNV frequencies found in the home-acquired nasal swab. The y-axis represents iSNV frequencies found the clinic-acquired combined throat and nasal swab. Dashed line is a one to …
Figure 3 with 1 supplement
Between host dynamics of IAV.
(A) The distribution of pairwise L1-norm distances for household (blue) and randomly-assigned community (gold) pairs. The bar heights are normalized to the height of the highest bar for each given …
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Figure 3—source data 1
Genetic distance of household and community sample pairs.
- https://doi.org/10.7554/eLife.35962.021
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Figure 3—source data 2
Day of onset and meta data for transmission pairs.
- https://doi.org/10.7554/eLife.35962.022
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Figure 3—source data 3
Frequencies of iSNV identified in transmission pairs.
- https://doi.org/10.7554/eLife.35962.023
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Figure 3—source data 4
The model prediction of the probability of transmission given donor frequency for the presence-absence model.
- https://doi.org/10.7554/eLife.35962.024
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Figure 3—source data 5
The frequency of donor iSNV used in fitting transmission models.
- https://doi.org/10.7554/eLife.35962.025
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Figure 3—source data 6
The model prediction of the probability of transmission given donor frequency for the beta-binomial model.
- https://doi.org/10.7554/eLife.35962.026
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Figure 3—source data 7
Bottleneck estimates for all isolate pairings in cases where multiple donor or recipient isolates are available.
SPECID refers to specimen ID. Those beginning in M were taken at the clinic. Those beginning with HS were isolated at home.
- https://doi.org/10.7554/eLife.35962.027
Figure 3—figure supplement 1
Estimate of effective bottleneck size with relaxed variant calling criteria.
(A) The frequency of iSNV in both recipient and donor isolates. iSNV were identified using the original variant calling pipeline as in (McCrone and Lauring, 2016). (B) The presence-absence model fit …
Tables
Table 1
Influenza viruses over five seasons in a household cohort
https://doi.org/10.7554/eLife.35962.002| 2010–2011 | 2011–2012 | 2012–2013 | 2013–2014 | 2014–2015 | |
|---|---|---|---|---|---|
| Households | 328 | 213 | 321 | 232 | 340 |
| Participants | 1441 | 943 | 1426 | 1049 | 1431 |
| Vaccinated, n (%)* | 934 (65) | 554 (59) | 942 (66) | 722 (69) | 992 (69) |
| IAV Positive Individuals† | 86 | 23 | 69 | 48 | 166 |
| H1N1 | 26 | 1 | 3 | 47 | 0 |
| H3N2 | 58 | 22 | 66 | 1 | 166 |
| IAV Positive Households‡ | |||||
| Two individuals | 13 | 2 | 9 | 7 | 23 |
| Three individuals | 5 | 2 | 3 | 3 | 11 |
| Four individuals | - | - | 1 | 2 | 4 |
| High Quality NGS Pairs§ | 4 | 1 | 2 | 6 | 39 |
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*Self reported or confirmed receipt of vaccine prior to the specified season.
†RT-PCR confirmed infection.
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‡Households in which two individuals were positive within 7 days of each other. In cases of trios and quartets, the putative chains could have no pair with onset > 7 days apart.
§Samples with > 103 genome copies per µl of transport medium, adequate amplification of all eight genomic segments, and average sequencing coverage > 103 per nucleotide.
Additional files
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Supplementary file 1
Sensitivity and specificity of variant detection
- https://doi.org/10.7554/eLife.35962.028
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Supplementary file 2
Nonsynonymous substitutions in HA antigenic sites
- https://doi.org/10.7554/eLife.35962.029
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Supplementary file 3
Estimated bottleneck size for individual transmission pairs
- https://doi.org/10.7554/eLife.35962.030
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Transparent reporting form
- https://doi.org/10.7554/eLife.35962.031
