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Human immunodeficiency virus type-1 (HIV-1) infection requires binding of the envelope protein gp120 to host CD4 receptors and the action of the chemokine receptors CXCR4 or CCR5, which define cell tropism. The proline-containing V3 loop of gp120 determines the selection of the chemokine receptor and participates in conformational changes on binding of gp120 to CD4. In this study, we show that macrophage-tropic and T-cell-tropic V3 loop peptides bind specifically to the active site of the immunophilins FK506-binding protein (FKBP12), and cyclophilins A and B. Macrophage-tropic and T-cell-tropic V3 loop peptides inhibited the peptidyl-prolyl cis-trans isomerase (PPIase) activities of the immunophilins. K d values in the range 0.036Ϫ4.1 µM were determined with V3 loop peptides labeled with an environmentally sensitive fluorophore. The observed binding properties of the V3 loop peptides reveal structural motifs of linear water-soluble peptidic substrates for tight interaction with immunophilins. FKBP12, and cyclophilins A and B were found to be present in normal human blood in the ranges 0.8Ϫ 1.7, 1.4Ϫ2.3 and 2.4Ϫ3.1 nM, respectively, as demonstrated by PPIase activity measurements and western blot analysis. Cyclophilins A and B levels in serum of HIV-1Ϫinfected individuals were increased 3.6-fold and 1.6-fold. Due to the interaction of immunophilins with V3 loop peptides and with the envelope protein gp120, a role of immunophilins in HIV pathogenesis as conformases or docking mediators seems possible, since immunophilin receptors on cell membranes and immunophilin-related virulence factors of pathogens have been identified.Keywords : human-immunodeficiency-virus-type-1 envelope protein gp120; V3 loop ; cyclophilin; FK506-binding protein; serum immunophilin.Human immunodeficiency virus type-1 (HIV-1) infects host exhibit peptidyl-prolyl cis-trans isomerase (PPIase) activity, cells via docking of its envelope glycoprotein gp120 to CD4 which is inhibited specifically and efficiently on binding of the receptors [1,2]. As a prerequisite for viral penetration, gp120 corresponding immunosuppressant. Several isoforms of the two has to undergo conformational changes in which the proline-families are known in eucaryotes and procaryotes. Some of them containing V3 loop of gp120 is involved. CD4 receptor binding act, in addition to their function as intracellular receptors of the provokes a conformational change in gp120, as measured by immunosuppressants, as catalysts of protein folding and as chapantibody epitope changes. However, this change alone was erones by stabilizing proteins in a defined conformation [8, 9]. found to be insufficient for viral entry. In addition to CD4 recep-A variety of bacterial and protozoan pathogens express FKBPtors, HIV-1 infection requires the participation of cell-tropic re-related PPIase termed macrophage-infectivity potentiators ceptors, either the A-chemokine receptor CXCR4 or the β-che-(Mip). Mip proteins act in host cell infection as virulence mokine receptor CCR5. The recognition site f...

In the course of the apoptotic cell death, cells fragment into apoptotic bodies, the elimination of which by phagocytosis is thought to avoid the release of cytosolic constituents whose occurrence is indicative for necrotic cell death. Confluent cultures of chicken embryo fibroblasts, however, show a different behaviour. After serum deprivation, they transiently released with the same time course mitogenic activity, lactate dehydrogenase and cytosolic peptidyl prolyl cis-trans isomerases into the serum-free culture medium. The release correlated in time with a decrease of the cell number which started approximately 3 h after serum removal and ceased within approximately 10 h at about half of the initial cell density. Morphological features like cell shrinkage, membrane blebbing and cell fragmentation as well as internucleosomal DNA fragmentation indicated apoptotic cell death whereas necrotic cell death could be excluded. Conditioned medium (M(r) > or = 30 kDa) from serum-deprived cultures of chicken embryo fibroblasts completely prevented chicken embryo fibroblasts to undergo apoptosis as did phorbol 12-myristate, 13-acetate and, to -60%, L-cysteine. Cycloheximide had no effect on serum deprivation-induced apoptosis. From the present results it can be concluded that chicken embryo fibroblasts and possibly other cells undergoing apoptosis release cytosolic components and endogenous survival factor(s) which prevent apoptosis.