Genetic variation was extensively studied for patient F78 as several samples were available throughout his entire 27-month infection period, including samples collected the same day in the URT and LRT. A phylogenetic tree ( Figure 3A ) performed with 11 complete genome sequences showed that the URT and LRT (1). The mutation rate then slowed down shortly before the patient's death (4.3610 7 and 1.3610 8 viral copy/ml for the last URT and LRT, respectively), despite a high viral load at the end of our follow-up period. This may account for the overall slower mutation rate calculated for this patient when compared with those infected for a shorter period ( Table 1 ). The last three samples collected simultaneously in both the URT and LRT were further analyzed by high throughput sequencing to compare variation at the minority population level ($5% of the total population). Most minority variants present in the LRT after 26.6 months persisted in this site, but were absent in the corresponding URT viral populations ( Figure 3B) . A similar observation was made with the majority variants and demonstrates that the genomes of the URT and Figure 3C ). Specific synonymous changes were found in both the URT and LRT sequences. However, non-synonymous changes were observed only in the LRT where we identified one change in the 59UTR polypyrimidine tract [44] , one non-synonymous change in the VP2 immunogenic site 2, and one non-synonymous change in protein 2A [32, 45] .