Immunodeficiency virus cDNA synthesis in resting T lymphocytes is regulated by T cell activation signals and dendritic cells.
We explored the relationship between T cell activation signals and dendritic cells (DC) in the replication cycle of immunodeficiency viruses. First we analyzed the effect of two cell cycle inhibitors (mimosine and aphidicolin) on SIV reverse transcription, circularization, and integration in macaque resting T cells stimulated with anti-CD3 mAb at the time of infection. The formation of SIV LTR circles was blocked by the G1 inhibitor mimosine. The G1/S inhibitor aphidicolin neither affected circularization nor integration of SIV DNA. Therefore, the induction of SIV LTR circle production is likely to be mediated by signaling events normally regulating the G1 to S transition. We further characterized DC-dependent HIV-expression in human T cells. We examined the effect of ligating two novel receptors, IPO-3 and Bgp95, on DC-dependent HIV-1 expression. Activation of DCs through IPO-3 receptors, and to a lesser extent Bgp95 ligation, upregulated HIV spread in these cells. The mechanisms by which IPO-3 vs. Bgp95 increase HIV-1 levels appear to be different. In particular, IPO-3 ligation alone on T cells also increased HIV-1 levels. Activation of T cells via defined surface receptors or with DCs is required for establishing HIV/SIV cDNA synthesis in T cells.
Polacino
P S
PS
Washington Regional Primate Research Center, University of Washington, Seattle 98195, USA.
Pinchuk
L M
LM
Sidorenko
S P
SP
Clark
E A
EA
D000818:Animals; D016590:Aphidicolin / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D004261:DNA Replication; D018076:DNA, Complementary / Q000096:biosynthesis; D004279:DNA, Viral / Q000096:biosynthesis*; D003713:Dendritic Cells / Q000276:immunology*; D005434:Flow Cytometry; D006678:HIV / Q000302:isolation & purification / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D008213:Lymphocyte Activation; D008253:Macaca mulatta; D008898:Mimosine / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism; D012091:Repetitive Sequences, Nucleic Acid; D015398:Signal Transduction; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000502:physiology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000821:virology*; D016662:Virus Integration; D014779:Virus Replication
D018076:DNA, Complementary; D004279:DNA, Viral; D016590:Aphidicolin; D008898:Mimosine; D012194:RNA-Directed DNA Polymerase