Evidence that T cell activation is required for HIV-1 entry in CD4+ lymphocytes.
The relationship of T cell activation to HIV entry and generation of viral DNA intermediates was studied in freshly isolated CD4+ T lymphocytes. Unstimulated cells exposed to infectious virus for up to 48 h did not synthesize any detectable unintegrated HIV DNA duplex forms or integrated genomic provirus. However, activation of these cells with either PHA or OKT3 (anti-CD3) mAb before viral exposure resulted in the generation of unintegrated HIV DNA after 6 h and integrated copies after 24 h. Cell-to-cell fusion studies showed significantly attenuated fusion between freshly isolated resting T cells and T cells constitutively expressing high levels of HIV envelope glycoprotein (HXB/gpt) compared with T cells first stimulated with either PHA or OKT3 mAb. The baseline fusion observed with resting T cells is believed to be a consequence of allogeneic stimulation by the HXB/gpt cell line. These results provide evidence that HIV entry and HIV envelope-dependent cell-to-cell fusion require T cell activation.
Gowda
S D
SD
Department of Pathology, Stanford University School of Medicine, CA 94305.
Stein
B S
BS
Mohagheghpour
N
N
Benike
C J
CJ
Engleman
E G
EG
D000945:Antigens, Differentiation, T-Lymphocyte; D002213:Capsid / Q000502:physiology; D002461:Cell Line, Transformed; D004279:DNA, Viral / Q000096:biosynthesis; D005814:Genes, Viral; D015497:HIV-1 / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D006801:Humans; D008213:Lymphocyte Activation; D008561:Membrane Fusion; D010641:Phenotype; D010835:Phytohemagglutinins; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism / Q000382:microbiology*; D014760:Viral Fusion Proteins / Q000276:immunology / Q000502:physiology
D000945:Antigens, Differentiation, T-Lymphocyte; D004279:DNA, Viral; D010835:Phytohemagglutinins; D014760:Viral Fusion Proteins