Infection of CD4+ memory T cells by HIV-1 requires expression of phosphodiesterase 4

Using PCR to monitor HIV-1 RNA genome reverse transcription and nuclear import of preintegration complexes, we found that memory, but not naive, CD4(+) T cells could support transport of HIV-1 DNA to nuclei upon TCR/CD3 and IL-2 stimulation. Moreover, memory CD4(+) T cells, unlike naive CD4(+) T cells, express high levels of phosphodiesterase 4 (PDE4) constitutively. Selective blocking of PDE4 activity inhibited IL-2R expression and thereby led to abolishing HIV-1 DNA nuclear import in memory T cells; however, full-length viral DNA synthesis was not affected. Thus, blocking PDE4 prevents initiation of HIV-1 DNA circle formation in T cells. The fact that PDE4 is expressed constitutively at higher levels in memory vs naive CD4(+) T cells may help HIV-1 readily infect memory T cells.