Figure 6. SIV DNA persistence does not require reinfection.

Several mechanisms have been postulated for the persistence of HIV DNA under prolonged therapy. (A) Infected cells harbouring HIV DNA may be long-lived, or (B) may undergo homeostatic replication, in which the daughter cell carries the HIV DNA. Panel C illustrates one possible mechanism of viral persistence under therapy, where latent cells become reactivated, shed virus and die, leading to the infection of a new generation of cells. However, during active infection (D), activation of latent WT infected cells (red) leads to production of small amounts of WT virus (red) that is effectively diluted by the abundance of EM virus in plasma (blue). Thus, reinfection is predominantly with EM virus, and the WT is effectively removed by activation and replication. The long-term persistence of WT SIV-DNA despite EM dominance in plasma, at levels at or above the AUC estimate (in animals 9021, 9175, 5424, 8020) make reinfection a very unlikely contributor to SIV DNA persistence.