Viral expansion after transfer is a primary driver of influenza A virus transmission bottlenecks

Abstract

For many viruses, narrow bottlenecks acting during transmission sharply reduce genetic diversity in a recipient host relative to the donor. Since genetic diversity represents adaptive potential, such losses of diversity are though to limit the opportunity for viral populations to undergo antigenic change and other adaptive processes. Thus, a detailed picture of evolutionary dynamics during transmission is critical to understanding the forces driving viral evolution at an epidemiologic scale. To advance this understanding, we used a novel barcoded virus library and a guinea pig model of transmission to decipher where in the transmission process diversity is lost for influenza A viruses. In inoculated guinea pigs, we show that a high level of viral genetic diversity is maintained across time. Continuity in the barcodes detected furthermore indicates that stochastic effects are not pronounced within inoculated hosts. Importantly, in both aerosol-exposed and direct contact-exposed animals, we observed many barcodes at the earliest time point(s) positive for infectious virus, indicating robust transfer of diversity through the environment. This high viral diversity is short-lived, however, with a sharp decline seen 1-2 days after initiation of infection. Although major losses of diversity at transmission are well described for influenza A virus, our data indicate that events that occur following viral transfer and during the earliest stages of natural infection have a predominant role in this process. This finding suggests that immune selection may have greater opportunity to operate during influenza A transmission than previously recognized.

Barcoded SARS-CoV-2 viruses define the impact of time and route of transmission on the transmission bottleneck in a Syrian hamster model

“…Virus transmission can be conceptualized as a series of bottlenecks, including but not limited to transfer to a new host and expansion within that host. A recent study by Holmes et al 22 using BC influenza reported much higher BC counts in contact animals 1-2 days post-exposure than at later timepoints, demonstrating that expansion is a major bottleneck in influenza transmission. To assess whether expansion also imposes a bottleneck on SARS-CoV-2 transmission, we collected the respiratory tissues from airborne-exposed contact hamsters 24 and 48hpe ( Fig.…”

“…These findings also highlight differences between SARS-CoV-2 and other respiratory viruses. As mentioned above, in influenza transmission, expansion in contacts is a stringent bottleneck 22 . We detected no evidence of a bottleneck during expansion in SARS-CoV-2 ( Fig S3 ).…”

“…These shortcomings necessitate the development of animal models where the transmission bottleneck can be studied quantitatively. Barcoded (BC) viruses containing a fitness-neutral genetic barcode have been effectively used to study virus transmission for an array of respiratory and non-respiratory viruses 19 , including influenza [20][21][22][23][24][25] , HIV and SIV [26][27][28][29][30][31][32] , Zika virus [33][34][35][36] , West Nile Virus 37 , and Coxsackie virus 38 . BC viruses overcome many of the shortcomings of measuring transmission by using iSNVs.…”