Human immunodeficiency virus type 1 T-lymphotropic strains enter macrophages via a CD4- and CXCR4-mediated pathway: replication is restricted at a postentry level.
The human immunodeficiency virus type 1 (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 CD4 and by stromal cell-derived factor 1alpha, 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.
Schmidtmayerova
H
H
The Picower Institute for Medical Research, Manhasset, New York 11030, USA. hsch@picower.edu
Alfano
M
M
Nuovo
G
G
Bukrinsky
M
M
D015704:CD4 Antigens / Q000276:immunology*; D002478:Cells, Cultured; D015658:HIV Infections / Q000276:immunology* / Q000821:virology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008214:Lymphocytes / Q000276:immunology / Q000821:virology*; D008264:Macrophages / Q000276:immunology / Q000821:virology*; D019718:Receptors, CXCR4 / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D014779:Virus Replication / Q000276:immunology
D015704:CD4 Antigens; D019718:Receptors, CXCR4