HIV-1 Vpr displays natural protein-transducing properties: implications for viral pathogenesis.

摘要: Abstract The 14-kDa Vpr protein of human immunodeficiency virus type 1 (HIV-1) serves multiple functions in the retroviral life cycle, including enhancement viral replication nondividing macrophages, induction G2 cell-cycle arrest proliferating T lymphocytes, and modulation HIV-1-induced apoptosis. Extracellular has been detected sera cerebral spinal fluid HIV-infected patients. However, it is not known whether such forms are biologically active. contains a carboxy-terminal basic amino acid rich segment stretch that homologous to domains mediate energy- receptor-independent cellular uptake polypeptides by process termed transduction. Similar functional protein-transducing present HIV-1 Tat, herpes simplex virus-1 DNA-binding VP22, Drosophila antennapedia homeotic transcription factor. We now demonstrate effective transduction active, synthetic (sVpr) as well Vpr-β-galactosidase fusion protein. contrast other transducing proteins, enhanced denaturation, Vpr's domain alone sufficient for its across biological membranes. In contrast, full-length effectively transduces broad array cells, leading dose-dependent Addition into extracellular medium also rescues Vpr-deficient strains macrophage cultures. Native may thus be optimized transduction, feature might enhance extend pathological effects HIV infection.