Bull James J, Koelle Katia, Antia Rustom
Department of Biological Sciences, University of Idaho, Moscow, ID, USA.
Department of Biology, Emory University, Atlanta, GA, USA.
Evol Med Public Health. 2025 Jan 31;13(1):101-110. doi: 10.1093/emph/eoaf002. eCollection 2025.
Viruses differ in the number and types of host tissues in which they replicate. For example, systemically replicating viruses such as measles infect cells and tissues throughout the body, whereas respiratory viruses such as influenza viruses and coronaviruses replicate only in the respiratory tract. Reinfections with respiratory viruses are thought to be driven by ongoing antigenic immune escape in the viral population. However, this does not explain why antigenic variation is frequently observed in respiratory viruses and not systemically replicating viruses. Here, we argue that the rapid rate of waning immunity in the respiratory tract is a key driver of antigenic evolution in respiratory viruses. Waning immunity results in hosts with immunity levels that protect against homologous reinfection but are insufficient to protect against infection with an antigenically different (heterologous) strain. Thus, when partially immune hosts are present at a high enough density, an immune escape variant can invade the viral population even though that variant cannot infect solidly immune hosts. Invasion can occur even when the variant's immune escape mutation incurs a fitness cost, although any such cost is likely to be short-lived from compensatory evolution. Thus, the mutant lineage may replace the wild type and, as immunity to it builds, the process will repeat. Our model provides a new explanation for the pattern of successive emergence and replacement of antigenic variants that has been observed in many respiratory viruses. We discuss our model relative to others for understanding the drivers of antigenic evolution in respiratory viruses.
病毒在其复制的宿主组织的数量和类型上存在差异。例如，像麻疹这样进行全身复制的病毒会感染全身的细胞和组织，而像流感病毒和冠状病毒这样的呼吸道病毒仅在呼吸道中复制。呼吸道病毒的再次感染被认为是由病毒群体中持续的抗原性免疫逃逸所驱动的。然而，这并不能解释为什么在呼吸道病毒中经常观察到抗原变异，而在全身复制的病毒中却没有。在这里，我们认为呼吸道中免疫消退的快速速率是呼吸道病毒抗原进化的关键驱动因素。免疫消退导致宿主的免疫水平能够预防同源再次感染，但不足以预防感染抗原性不同（异源）的毒株。因此，当部分免疫的宿主以足够高的密度存在时，即使该变异株不能感染完全免疫的宿主，一个免疫逃逸变异株也能够侵入病毒群体。即使变异株的免疫逃逸突变带来了适应性代价，入侵也可能发生，尽管任何这样的代价可能会因补偿性进化而短暂存在。因此，突变谱系可能会取代野生型，并且随着对其免疫力的增强，这个过程会重复。我们的模型为在许多呼吸道病毒中观察到的抗原变异株连续出现和取代的模式提供了一种新的解释。我们将我们的模型与其他模型进行了讨论，以理解呼吸道病毒抗原进化的驱动因素。
