Generation of HIV latency during thymopoiesis

The use of combination antiretroviral therapy results in a substantial redu ction in viremia, a rebound of CD4(+) T cells and increased survival for HI V-infected individuals. However, this treatment does not result in the tota l eradication of HIV. Rather, the virus is thought to remain latent in a su bset of cells, where it avoids elimination by the immune system. In this st ate the virus is capable of reactivation of productive infection following cessation of therapy. These latently infected cells are very few in number and it has thus been difficult to determine their origin and to study the m olecular nature of the latent viral genome. HIV replication is linked to ce llular gene transcription and requires target cell activation. Therefore, s hould an activated, infected cell become transcriptionally inactive prior t o cytopathic effects, the viral genome might be maintained in a latent stat e. We used the SCID-hu (Thy/Liv) mouse model to establish that activation-i nducible HIV can be generated at high frequency during thymopoiesis, a proc ess where previously activated cells mature towards quiescence. Moreover, w e showed that these cells can be exported into the periphery where the viru s remains latent until T-cell receptor stimulation, indicating that the thy mus might be a source of latent HIV in humans.