Human CD38 interferes with HIV-1 fusion through a sequence homologous to the V3 loop of the viral envelope glycoprotein gp120.

CD38 is a progression marker in HIV-1 infection, it displays lateral association with CD4, and down-modulates gp120/CD4 binding. The aim of this study was to elucidate the mechanism behind the interplay between CD4, CD38, and HIV-1. We used mouse cell transfectants expressing human CD4 and either CD38 or other CD4-associated molecules to show that CD38 specifically inhibits gp120/CD4 binding. Human cell transfectants expressing truncated forms of CD38 and bioinformatic analysis were used to map the anti-HIV activity and show that it is concentrated in the membrane-proximal region. This region displayed significant sequence-similarity with the V3 loop of the HIV-1 gp120 glycoprotein. In line with this similarity, synthetic soluble peptides derived from this region reproduced the anti-HIV effects of full-length CD38 and inhibited HIV-1 and HIV-2 primary isolates from different subtypes and with different coreceptor use. A multiple-branched peptide construct presenting part of the sequence of the V3-like region potently and selectively inhibited HIV-1 replication in the nanomolar range. Conversely, a deletion in the V3-like region abrogated the anti-HIV-1 activity of CD38 and its lateral association with CD4. These findings may provide new insights into the early events of HIV-1 fusion and strategies to intervene.

[Histogenic characterization of the cells forming RA pannus]. / Caratterizzazione istogenetica dei pannociti nell'artrite reumatoide.

OBJECTIVE: This work aims to clarify the histogenesis of the cells forming RA pannus: the pannocytes. METHODS: 15 patients with seropositive RA; 5 controls with post-traumatic knee effusion and 5 with OA knee effusion were included in the study. Synovial tissues and fluids, collected during diagnostic arthrocentesis, were used as a source of cells to be cultured. Viable staining and cytocentrifugation were performed. Cell phenotype was investigated by immunofluorescence assays after different culture periods. Cells were also studied by immunohistochemistry to determine the presence of CD5, CD68:KP-1, CD68:PG-M1, vimentin, cytokeratin, a-SM-Actin. RESULTS: Cells derived from RA samples were sub-divided into two population of lymphocyte-like and macrophage-like cells. Phenotypical characteristics of the first one were analysed after 6 days of culture and suggested they were T lymphocytes. The other population could grow in vitro for undefined time resembling the neoplastic-like proliferation previously described for pannocytes. Phenotypic characterization excluded that these cells were lymphocytes, monocyte-macrophages, fibroblasts, myofibroblasts, endothelial cells or keratinocytes. On the contrary, immunohistochemistry demonstrated that 100% of pannocytes were vimentin positive and 75% of these cells expressed also CD68:KP-1. CONCLUSIONS. The results exclude that pannocytes originate from monocyte-macrophages or from fibroblasts, but strongly support the hypothesis that they belong to the family of primitive embryonal connective tissue-forming cells (residue of the primitive mesenchymal tissue).