Biology subjects

Holmes, K. E.

Publications and source records attributed to Holmes, K. E..

4 recordsLinked to original sources

bioRxiv2023

Ventilation does not affect influenza virus transmission efficiency in a ferret playpen setup

Sustained community spread of influenza viruses relies on efficient person-to-person transmission. Current experimental transmission systems do not mimic environmental conditions (e.g., air exchange rates, flow patterns), host behaviors or exposure durations relevant to real-world settings. Therefore, results from these traditional systems may not be representative of influenza virus transmission in humans. To address this pitfall, we developed a modified, more realistic transmission setup and used it to investigate the impact of ventilation rates on transmission in a close-range, play-based scenario. In this setup, four immunologically naive recipient ferrets were exposed to a donor ferret infected with a genetically barcoded 2009 H1N1 virus (H1N1pdm09) for four hours. The ferrets interacted in a shared space that included toys, similar to a child care setting. The transmission efficiency was determined under conditions of low and high ventilation rates; air exchange rates of [~] 1.3 hr-1 and 23 hr-1, respectively. Despite the large difference in ventilation rate, transmission efficiency was the same, 50% in two independent replicate studies. The presence of infectious virus or viral RNA on surfaces and in air throughout the exposure area was similar regardless of ventilation rate. While high viral genetic diversity in donor ferret nasal washes was maintained during infection, recipient ferret nasal washes displayed low diversity, revealing a narrow transmission bottleneck regardless of ventilation rate. Our findings indicate that in exposures characterized by frequent close-range, play-based interactions and the presence of fomites, ventilation does not significantly impact transmission efficiency. SignificanceImproved ventilation in building has the potential to reduce transmission of respiratory viruses, but its effect in different settings is not well understood. We developed a novel system to study influenza virus transmission in the ferret animal model in an environment that mimics a child care center. We demonstrate that increased ventilation is not effective at disrupting transmission in this setting, suggesting that transmission occurs mainly at close-range or via fomites. Multiple interventions are needed to reduce the spread of influenza virus in this type of setting.

microbiology↗

bioRxiv2023

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

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 thought 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 barcoded virus library and a guinea pig model of transmission to decipher where in the transmission process influenza A virus populations lose diversity. In inoculated guinea pigs, we show that a high level of viral barcode diversity is maintained. Within-host continuity in the barcodes detected across time furthermore indicates that stochastic effects are not pronounced within the inoculated hosts. Importantly, in both aerosol-exposed and direct contact 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 central role in this process. This finding suggests that host factors, such as immune effectors, may have greater opportunity to impose selection during influenza A virus transmission than previously recognized.

microbiology↗

bioRxiv2022

Influenza A virus coinfection dynamics are shaped by distinct virus-virus interactions within and between cells

When multiple viral populations propagate within the same host environment, they often shape each others dynamics. These interactions can be positive or negative and can occur at multiple scales, from coinfection of a cell to co-circulation at a global population level. For influenza A viruses (IAVs), the delivery of multiple viral genomes to a cell substantially increases burst size. However, despite its relevance for IAV evolution through reassortment, the implications of this positive density dependence for coinfection between distinct IAVs has not been explored. Furthermore, the extent to which these interactions within the cell shape viral dynamics at the level of the host remains unclear. Here we show that, within cells, coinfecting IAVs strongly augment the replication of a focal strain, irrespective of the native host of the coinfecting IAV or its homology to the focal strain. Coinfecting viruses with a low intrinsic reliance on multiple infection offer the greatest benefit. Nevertheless, virus-virus interactions at the level of the whole host are antagonistic. This antagonism is recapitulated in cell culture when the coinfecting virus is introduced several hours prior to the focal strain or under conditions conducive to multiple rounds of viral replication. Together, these data suggest that beneficial virus-virus interactions within cells are counterbalanced by competition for susceptible cells during viral propagation through a tissue. The integration of virus-virus interactions across scales is critical in defining the outcomes of viral coinfection.

microbiology↗

bioRxiv2021

Timing of exposure is critical in a highly sensitive model of SARS-CoV-2 transmission

Transmission efficiency is a critical factor determining the size of an outbreak of infectious disease. Indeed, the propensity of SARS-CoV-2 to transmit among humans precipitated and continues to sustain the COVID-19 pandemic. Nevertheless, the number of new cases among contacts is highly variable and underlying reasons for wide-ranging transmission outcomes remain unclear. Here, we evaluated viral spread in golden Syrian hamsters to define the impact of temporal and environmental conditions on the efficiency of SARS-CoV-2 transmission through the air. Our data show that exposure periods as brief as one hour are sufficient to support robust transmission. However, the timing after infection is critical for transmission success, with the highest frequency of transmission to contacts occurring at times of peak viral load in the donor animals. Relative humidity and temperature had no detectable impact on transmission when exposures were carried out with optimal timing. However, contrary to expectation, trends observed with sub-optimal exposure timing suggest improved transmission at high relative humidity or high temperature. In sum, among the conditions tested, our data reveal the timing of exposure to be the strongest determinant of SARS-CoV-2 transmission success and implicate viral load as an important driver of transmission.

microbiology↗