Establishment of latent HIV-1 infection of resting CD4(+) T lymphocytes does not require inactivation of Vpr

The introduction of highly active antiretroviral therapy (HAART) for the tr eatment of HIV-1 infection has allowed dramatic reductions in plasma virus levels to below the limit of detection in many patients. However, latently infected CD4(+) memory T lymphocytes persist as an important reservoir for the virus in the presence of this aggressive therapy and represent a major barrier to HIV-1 eradication with HAART. The mechanism through which the la tent compartment is formed has not yet been established. It may involve act ively proliferating CD4(+) T-cell intermediates that are infected with HIV- 1 and revert back to a resting state, carrying integrated provirus at some low frequency. The HIV-1 accessory protein Vpr, which mediates G(2) cell cy cle arrest in host cells, may interfere with the formation of the latently infected T cells by preventing them from exiting the cell cycle to return t o a resting state. To investigate the role of the Vpr in the formation of l atently infected memory T cells, we cloned and characterized vpr genes from viruses in the latent reservoir. Both sequence analysis and functional ass ays demonstrated that the vpr gene products of the Viruses isolated from th e latent pool did not differ significantly from those of a functional Vpr ( NL4-3). These results indicate that the generation of resting G(0) memory T lymphocytes that carry latent HIV-1 provirus occurs despite the G(2) arres t function of the vpr gene product. (C) 2000 Academic Press.