Model. Heterologous innate immunity creates a subset of individuals refractory to infection during periods of high respiratory virus circulation. (A) Virus 1 induces a mucosal IFN response, which creates a refractory period following infection during which ISGs are elevated and the host is protected from a second viral infection (red shading). After ISGs return to baseline, the host is again susceptible and can be infected with virus 2. (B) During periods of high respiratory virus circulation, a fraction of the population is refractory to infection at any given time due to ISG activation from a recent infection (red shaded figures). Thus, heterologous innate immune protection could mitigate against viral transmission at times of high respiratory virus circulation. Figure created with BioRender.com.