Speaker
Description
The use of barcoded SIV allows the tracking of individual viral lineages within infected rhesus macaques. Studies of clonal dynamics early after vaginal infection have demonstrated a surprising diversity in the sizes of founding lineages in individual animals within a couple weeks of infection (i.e., prior to any immune selection). This heterogeneity in lineage sizes early after infection (up to 103-fold differences) occurs even in low dose infection, where a small number of virions is estimated to seed infection. There are multiple potential mechanisms behind the observed heterogeneity in viral lineage size. For example, delays in crossing an anatomical barrier between the site of infection and systemic infection, and variability in the rate of spread of infection to peripheral tissues. However, similar heterogeneity was also observed after intravenous infection of rhesus macaques with barcoded virus, suggesting that other factors such as the seeding of anatomical or microanatomical niches may play a role. To explore this further, we analysed viral production from infected cells in vitro by analysing the production of individual barcodes in low MOI infection. Again, a high level of heterogeneity between production of individual barcodes was observed. Finally, we treated cells early after in vitro infection of the SupT1-R5 cell line to observe the diversity of viral production from individual cells. We observed that the levels of virus produced can vary by up to 103-fold, even after a single round of infection. This strongly implies that the high diversity in founding lineage sizes early after infection is driven by high variability in viral production rates by individual cells.
