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 treatment 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 latent compartment is formed has not yet been established. It may involve actively 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 cycle 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 to a resting state. To investigate the role of the Vpr in the formation of latently infected memory T cells, we cloned and characterized vpr genes from viruses in the latent reservoir. Both sequence analysis and functional assays demonstrated that the vpr gene products of the viruses isolated from the 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) arrest function of the vpr gene product.
Shen
A
A
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Siliciano
J D
JD
Pierson
T C
TC
Buck
C B
CB
Siliciano
R F
RF
D000595:Amino Acid Sequence; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000821:virology*; D002453:Cell Cycle; D002460:Cell Line; D003001:Cloning, Molecular; D016336:Gene Products, vpr / Q000235:genetics / Q000502:physiology*; D005814:Genes, Viral; D015497:HIV-1 / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D017735:Virus Latency; D014779:Virus Replication; D054325:vpr Gene Products, Human Immunodeficiency Virus
D016336:Gene Products, vpr; D054325:vpr Gene Products, Human Immunodeficiency Virus