HIV-1-mediated syncytium formation promotes cell-to-cell transfer of Tax protein and HTLV-I gene expression.
An important increase in luciferase activity was detected following co-culture of Jurkat T cells transiently transfected with an HTLV-I-LTR-driven reporter construct with HIV-1- and HTLV-I-infected cells. Production of infectious HTLV-I and expression of the HTLV-I envelope were not required for this HIV-1-dependent induction while it was severely hampered by anti-gp120 and anti-CD4 antibodies. The HTLV-I Tax protein and the TRE1 repeats were found to be necessary for the HIV-1-mediated enhancement of HTLV-I LTR activity in the co-culture assay. As these results suggested triple fusion events involving all three cell types and the intracellular transfer of Tax, we labelled each cell line with a distinct fluorescent probe. Through confocal microscopy, a number of resulting syncytia and cell clusters were indeed observed to be positive for all three probes. We are proposing a model in which HIV-1-mediated syncytium formation between HIV-1- and HTLV-I-infected cells and uninfected T cells forms a "bridge" or "tunnel" through which Tax from the HTLV-I-infected cells can diffuse and activate HTLV-I-LTR transcription.
Sun
Jiangfeng
J
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario and Faculty of Medicine, Laval University, Que., Canada.
Barbeau
Benoit
B
Tremblay
Michel J
MJ
D002460:Cell Line; D018920:Coculture Techniques; D015967:Gene Expression Regulation, Viral; D016356:Gene Products, tax / Q000378:metabolism*; D017930:Genes, Reporter; D015726:Giant Cells / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D006801:Humans; D008156:Luciferases / Q000235:genetics; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D021381:Protein Transport
D016356:Gene Products, tax; D008156:Luciferases