Inferring Transmission Bottleneck Size from Viral Sequence Data Using a Novel Haplotype Reconstruction Method.

Area of Science:

• Virology
• Evolutionary Biology
• Genetics

Background:

• The transmission bottleneck, the number of viral particles initiating a new infection, significantly impacts viral evolution.
• Previous estimates of the influenza virus transmission bottleneck using allele frequencies have limitations.
• Understanding the transmission bottleneck is crucial for comprehending viral population dynamics and evolution.

Purpose of the Study:

• To develop and apply a novel method for inferring viral transmission bottleneck sizes.
• To re-evaluate the transmission bottleneck of influenza A virus in human hosts.
• To assess the impact of the transmission bottleneck on within-host viral diversity.

Main Methods:

• A novel approach combining haplotype reconstruction algorithms with maximum likelihood methods was developed.
• The method allows for rapid calculation and robust inference of population bottlenecks.
• The approach was validated using simulated transmission events and applied to influenza A transmission data.

Main Results:

• The novel method accurately inferred transmission bottlenecks from simulated data, even with minor errors in haplotype reconstruction.
• Re-analysis of influenza A transmission data confirmed a small bottleneck, with 1 to 13 viral particles transmitted.
• The inferred bottleneck size was slightly larger than some previous estimates, suggesting a less extreme bottleneck.

Conclusions:

• The study confirms a small transmission bottleneck for influenza A virus between human hosts.
• The bottleneck, while tight, is not so restrictive as to completely eliminate the transmission of within-host viral diversity.
• The developed method provides a more robust approach for estimating viral transmission bottlenecks.