Human immunodeficiency virus type 1 T-lymphotropic strains enter macrophages via a CD4- and CXCR4-Mediated pathway: Replication is restricted at a post-entry level

The human immunodeficiency virus type I (HIV-1) laboratory strains adapted to T-cell lines, as well as most syncytium-inducing primary isolates, replicate poorly in macrophages, which, beside CD4(+) T lymphocytes, are major targets of HIV-1. In the present work we used a semiquantitative PCR-based technique to study viral entry into cells, kinetics of reverse transcription, and translocation of the viral DNA into the nucleus of macrophages infected with different HIV-1 strains, Our results demonstrate that T-lymphotropic strains efficiently enter macrophages, Entry was inhibited by a monoclonal antibody against CD I and by stromal cell-derived factor 1 alpha, a natural ligand of CXCR4, suggesting that both CD4 and CXCR4 act as receptors on macrophages for HIV-1 T-lymphotropic strains. Analysis of the kinetics of reverse transcription and nuclear import revealed that the most pronounced differences between T-lymphotropic and macrophagetropic strains occurred at the level of nuclear translocation of viral DNA, although a delay in reverse transcription was also observed. These results suggest that postentry steps are critical for restricted replication of T-lymphotropic HIV-1 strains in macrophages.