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PM Cannon, DG Tenen, MB Feinberg, HS Shin and S Kim
New England Deaconess Hospital, Boston, MA.
As a model system to study the infection of early myeloid cells by human
immunodeficiency virus-1 (HIV-1), we have infected the human promyelocytic
cell line, HL-60, with a recombinant selectable HIV-1 clone. A fully
infected population showed a relatively high frequency of low-level
infection, with 40% of subcloned cells being negative by reverse
transcriptase and p24 indirect immunofluorescence analysis and displaying
only low levels of supernatant p24. The same treatment of a T-lymphoid cell
line produced 100% productive infections. HIV-1 infection of HL-60 did not
appear to alter the state of differentiation of the cells, as assessed by
surface antigen expression, regardless of the level of viral expression.
Furthermore, infected cells were able to respond normally to chemical
inducers of differentiation. Induction of differentiation towards
monocyte/macrophages by phorbol myristate acetate activated the HIV-1 long
terminal repeat in a transient transfection system, and there was a
corresponding increase in viral production from the infected subclones.
Granulocytic differentiation, as stimulated by dimethyl sulfoxide or
retinoic acid, had no effect on long terminal repeat activity and did not
stimulate viral replication. These data suggest that low-level HIV-1
infections may be established at a relatively high frequency in myeloid
precursor cells, and that different pathways of promyelocytic
differentiation vary in their ability to stimulate HIV-1 replication.
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| Copyright © 1993 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||