Cross-scale dynamics and the evolutionary emergence of infectious diseases

Sebastian J. Schreiber; Ruian Ke; Claude Loverdo; Miran Park; Priyanna Ahsan; James O. Lloyd-Smith

Within-host scale model. Infection of a host usually starts locally at the site of viral entry or first tissue contact. This local spread involves a small number of viruses, their infection of host cells at the exposure interface and possibly the innate immune response to infection [81, 82] . During this period, infection is stochastic and establishment of infection is not guaranteed [82, 83] . When one or more virions survive the period of initial local spread, they establish lineages that comprise the productive infection. These virions are termed as transmitted founder viruses [44] . Here, we explicitly define the number of transmitted founder viruses that establish productive infection as the bottleneck width N . This quantity can be estimated using viral genetic sequencing data, for example in [44, 55] . Our within-host model starts with the transmitted founder viruses by assuming an initial viral load N , and hence considers the period of established productive infection only (as with other within-host models [84, 85] and cross-scale deterministic models [73] ). The initial viral exposure and stochastic local infection process are implicitly incorporated into the transmission term in the population scale model as described below, and consequently, we consider a successful transmission event as a transmission event leading to an established infection.