Holmes Katie E, Ferreri Lucas M, Elie Baptiste, Ganti Ketaki, Lee Chung-Young, VanInsberghe David, Lowen Anice C
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GeorgiaUnited States of America.
Department of Microbiology, School of Medicine, Kyungpook National University, Jung-gu, Daegu, Republic of Korea.
PLoS Biol. 2025 Sep 2;23(9):e3003352. doi: 10.1371/journal.pbio.3003352. eCollection 2025 Sep.
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.
对于许多病毒而言，传播过程中起作用的狭窄瓶颈会大幅降低受体宿主相对于供体宿主的遗传多样性。由于遗传多样性代表着适应潜力，这种多样性的丧失被认为会限制病毒群体发生抗原变化和其他适应过程的机会。因此，详细了解传播过程中的进化动态对于理解在流行病学规模上驱动病毒进化的力量至关重要。为了深化这一理解，我们使用了一个条形码病毒库和豚鼠传播模型来解读甲型流感病毒群体在传播过程中的何处丧失多样性。在接种的豚鼠中，我们发现病毒条形码多样性维持在较高水平。此外，随着时间推移检测到的条形码在宿主体内的连续性表明，接种宿主体内的随机效应并不明显。重要的是，在气溶胶暴露和直接接触的动物中，我们在最早的感染病毒阳性时间点观察到了许多条形码，这表明多样性通过环境实现了强劲转移。然而，这种高病毒多样性是短暂的，在感染开始后的1 - 2天内就出现了急剧下降。虽然甲型流感病毒在传播时多样性的主要丧失情况已有充分描述，但我们的数据表明，病毒转移后以及自然感染最早阶段发生的事件在这一过程中起着核心作用。这一发现表明，宿主因素，如免疫效应器，在甲型流感病毒传播期间施加选择的机会可能比之前认为的更大。
