Temporal evolution of HTLV-1 clonal structure in natural infection. (A) Proviral load in PBMCs in 11 patients during follow-up for 5 to 9 years. (B) Clonality analysis was made in triplicate at time 1 (t1, A, □) and time 2 (t2, A, ○). Oligoclonality index increased with time in patients with nonmalignant infection (paired t test, P = .017). In March 2007, the oligoclonality index of patient TBK (black line) reached the range typical of ATLL (Figure 2A-B) and lymphoma-type ATLL was subsequently diagnosed in June 2009. (C) □ represents the percentage of the PVL at time 1 that was constituted by UISs, which were detected again at time 2; and ○, the percentage of PVL at time 2 constituted by UISs that had been detected at time 1. (D) The majority of large UISs (those that constituted the top quartile of the PVL) at time 2 were already large (top quartile of PVL) at time 1 (solid black bars). (E) Newly detected UISs at time 2 were mainly small UISs (black fraction of the bars) and on average made up less than 20% of the total PVL. (F) Temporal variation in UIS abundance. S1 represents the abundance of a given UIS at time 1; and S2, the abundance at time 2. Low-abundance UISs became less abundant, whereas high-abundance UISs grew. Asterisks denote the significance of difference of the observed ratio (S1/S2) from 1.0 (t test). Sample size: 0.1 and below, n = 3979; 0.1 to 1, n = 12 463; 1 to 5, n = 1016; 5 to 10, n = 52; and 10 and above, n = 21. ***P < .001. *P < .05. NS indicates not significant (P > .05).