Viruses differ in the number and types of host tissues in which they replicate. 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.
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