Restricted replication of the HIV-1 T-lymphotropic isolate NL4-3 in HL-60 cells.
To understand how different cell types might influence the generation of viral variants, we have examined the differences in the viral life cycle of the HIV-1 isolate, NL4-3, in the human promyelocytic cell line, HL-60, and the human T cell line, H9. NL4-3 harvested from H9 cells productively infected and was cytopathic to H9 and HL-60 cells. However, the cytopathic effect was delayed in HL-60 cells compared to that seen in H9 cells, suggesting that NL4-3 replication was restricted in myeloid cells. This restriction was overcome by production of a variant virus, NL4-3 (M), which replicated efficiently in HL-60 cells. Measurements of the kinetics of entry of NL4-3 in H9 and HL-60 cells and NL4-3 (M) in HL-60 cells demonstrated that the timing of viral entry into each cell line was similar. However, quantitation of the amount of newly reverse-transcribed NL4-3 DNA in H9 and HL-60 cells revealed that NL4-3-infected H9 cells and NL4-3 (M)-infected HL-60 cells contained consistently more newly reverse-transcribed DNA than NL4-3-infected HL-60 cells. This difference was further amplified by inefficient spread of the virus throughout the HL-60 culture. Together these results suggest that the efficiency of NL4-3 infection of HL-60 cells is restricted at early steps in the viral life cycle and may be restricted at late steps as well.
Department of Molecular Genetics and Microbiology, University of Massachusetts Medical Center, Worcester.
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Pise-Masison
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Holland
D001483:Base Sequence; D002460:Cell Line; D003588:Cytopathogenic Effect, Viral; D017931:DNA Primers; D004279:DNA, Viral / Q000032:analysis; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008561:Membrane Fusion; D008969:Molecular Sequence Data; D013601:T-Lymphocytes / Q000821:virology*; D014779:Virus Replication
D017931:DNA Primers; D004279:DNA, Viral