ACCUMULATION OF UNINTEGRATED CIRCULAR VIRAL-DNA IN MONOCYTES AND GROWTH-ARRESTED T-CELLS FOLLOWING INFECTION WITH HIV-1

Cytocidal retrovirus infection is characterized by rapid accumulation of unintegrated viral DNA forms. These are thought to be generated by multiple rounds of reinfection and have been suggested to play a centr al role in cytopathogenesis. Here we have reviewed the work done in th is area with HIV-1, mostly using acutely and chronically infected T ce ll and monocytic cell lines and in some cases T cells blocked at S pha se of the cell cycle by aphidicolin treatment. To these studies, we ha ve compared our findings with HIV-1 infected primary peripheral blood monocyte-derived macrophages and untreated and growth-arrested MT-2 ce lls, two biologically disparate cell populations. Using 1- and 2-long terminal repeat (LTR) circular forms as indicators of unintegrated vir al DNA, we found similar rapid accumulation in both untreated and grow th-arrested MT-2 cells. In contrast, we found much lower levels in mon ocyte/macrophages. Our findings suggest that accumulation of unintegra ted viral DNA does not require virus production and reinfection in gro wth-arrested T cells. The significantly lower levels found in monocyte /macrophages may reflect superinfection resistance, allowing the maint enance of a persistent infection.