Complete genome sequences were obtained at different time points in the URT and/or LRT for the five chronically-infected lung transplant recipients ( Table 1 ). The number of substitutions per nucleotide and per day is reported in Table 1 for each patient, except for A46 for whom samples collected at different time points were not available. Calculated mutation frequencies ranged between 7.27610 26 and 3.88610 25 . No overlapping mutations in the URT or LRT were found between the five patients. However, superimposition of all changes along a reference genome (HRV-A2) (Figure 2A ) revealed that whereas synonymous changes were distributed along the genome without any apparent specific pattern, non-synonymous mutations were clustering mostly in the capsid genes VP2, VP3 and VP1, the first half of 2A genes, and in 3A genes. Cold spot regions were located in the viral capsid gene VP4, as well as in 2B, 2C, 3B, 3C, and most of 3D. Only three changes were found in the 59UTR and one in the 39UTR. The variation hot spots observed in the capsid genes were similar to the amino acid variability observed among HRV reference types ( Figure 2B ).