Characterization of human B cell (DK) and promonocyte (U937) clones after HIV-1 exposure: accumulation of viral reverse transcriptase activity in cells and early syncytia induction against SupT1 cells.
The kinetics of HIV-1 infection were compared among human B (DK), promonocyte (U937), T-B hybrid (CEMX174), and T (H9) cell lines. Just like H9 cells, CEMX174 cells exhibited strong syncytia induction capacity against highly HIV-1-sensitive CD4+ T cells (SupT1) and had high reverse transcriptase (RT) release in the supernatant. DK and U937 cells showed syncytia induction capacity by 72 hr, but RT activity in the culture supernatant (extracellular RT) increased much later. RT activity in cell lysates (intracellular RT) became detectable at 12-15 days. The inverted extracellular/intracellular RT ratio and syncytia induction capacity were also observed in chronically infected DK (DK-IIIB) and U937 (U937-IIIB) cell lines and subclones from U937-IIIB. Further, the coculture of H9 with DK-IIIB (which indicates no detectable extracellular RT release) showed remarkable amplification of extracellular RT with significant increase of T-B double marker hybrids (H9-DK-IIIB). Our results suggest that B cells and/or monocytes/macrophages may acquire fusing capacity against CD4+ T cells in early stages of the infection and that these cell-to-cell interactions may also lead to a reduction in the number of CD4+ T cells. Further, these T-B and T monocyte hybrids may serve as temporal sites for viral replication. These in vitro studies may provide clues to the possible immunopathological roles of HIV-1-infected B cells and monocytes/macrophages and may help in understanding the mechanisms of viral burden on an infected host.
Sei
Y
Y
Laboratory of Neuroscience, National Institutes of Health, Bethesda, Maryland 20892.
Inoue
M
M
Yokoyama
M M
MM
Bekesi
J G
JG
Arora
P K
PK
D001402:B-Lymphocytes / Q000382:microbiology*; D015704:CD4 Antigens / Q000378:metabolism; D002459:Cell Fusion; D002999:Clone Cells; D006678:HIV / Q000201:enzymology / Q000254:growth & development; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D015658:HIV Infections / Q000201:enzymology / Q000473:pathology*; D006801:Humans; D009000:Monocytes / Q000382:microbiology*; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism
D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D012194:RNA-Directed DNA Polymerase