1,721,086 research outputs found

    Infection of human T lymphoid cells by human herpesvirus 6 is blocked by two unrelated protein tyrosine kinase inhibitors, biochanin A and herbimycin

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    Human herpesvirus 6 is a T lymphotropic herpesvirus that causes exanthem subitum in infants and is considered a potential cofactor in AIDS etiopathogenesis and progression owing to its in vivo and in vitro interactions with human immunodeficiency virus, We report that no differences in phosphorylation on tyrosine residues of cellular proteins were detectable at early times following HHV-6 infection in comparison to uninfected cells, On the contrary, several cellular proteins appeared phosphorylated on tyrosine at 24-48 hr postinfection, In addition, when tyrosine phosphorylation induced by HHV-6 infection was inhibited by the tyrosine kinase inhibitor biochanin A, the infection of HSB-2 cells was also coordinately reduced, as judged by inhibition of cytopathic effect and by inhibition of early and late viral antigen expression, Similar results were obtained with a second unrelated tyrosine kinase inhibitor, herbimycin, The inhibitors seem to act at a late stage of the viral infectious cycle, since neither viral binding nor internalization were affected. Thus, our results indicate that HHV-6 infection leads to the phosphorylation of protein tyrosine kinases, which may play a role in the course of viral infection, probably by participating in the cytopathic effect induced by the virus

    CR2 units of CR2 complexes are possibly associated with nucleophilic agents through reactive covalent links

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    The human complement receptor type 2 (CR2/CD21), a transmembrane glycoprotein, associates with a variety of surface antigens and proteins in the cell membrane. We examined the possibilities that the CR2 units of CR2 complexes are associated through internal covalent links reactive with nucleophilic agents, e.g. H2O or methylamine, and that CR2-positive cells process anti-CR2 monoclonal antibodies (MoAbs). Data from immunoblotting and cytofluorimetry with CR2-binding site-specific MoAbs show that: (i) CR2-positive Raji cells release soluble CR2 isoforms into the medium when incubated in phosphate buffered saline; (ii) despite affecting the detection of one soluble CR2 isoform, methylamine treatment of soluble CR2 allows the detection of another of its isoforms; (iii) limited pre-treatment of cells with methylamine reveals a more heterogeneous CR2-positive cell population or enhances the detection of CR2; (iv) cell treatment with CR2-binding site-specific MoAbs enhances the detection of CR2 isoform(s). The data suggest that CR2 is shed mainly as a soluble CR2 complex, in which the CR2 units link covalently and react with nucleophilic agents. Raji cells may process bound fragments (145kDa) that are recognised by and become bound by anti-CR2 MoAb. © 2003 Elsevier Science Ltd. All rights reserved

    Interference with the Autophagic Process as a Viral Strategy to Escape from the Immune Control: Lesson from Gamma Herpesviruses

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    We summarized the most recent findings on the role of autophagy in antiviral immune response. We described how viruses have developed strategies to subvert the autophagic process. A particular attention has been given to Epstein-Barr and Kaposi's sarcoma associated Herpesvirus, viruses studied for many years in our laboratory. These two viruses belong to γ-Herpesvirus subfamily and are associated with several human cancers. Besides the effects on the immune response, we have described how autophagy subversion by viruses may also concur to the enhancement of their replication and to viral tumorigenesis

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Suppression of dendritic cell differentiation through cytokines released by Primary Effusion Lymphoma cells

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    Functional impairment of dendritic cells (DC) appears to be one of the mechanisms responsible for tumor escape from the control of the immune system. DC isolated from tumor-bearing animals and cancer patients with solid or with hematological malignancies have phenotypic and functional abnormalities. In addition, supernatants from in vitro cultured tumor cells have been shown to interfere with DC differentiation from CD34+ and monocyte precursors. Primary effusion lymphoma (PEL) is a Human Herpesvirus-8 (HHV-8)-associated tumor, which releases several cytokines such as IL-6, IL-10 and VEGF and its growth seems to be dependent on them in vitro or in vivo. In the present study, we found that these cytokines released by PELs have also an important role in interfering with the in vitro differentiation of immature DC (iDC) from CD14+ monocytes. The iDC obtained in the presence of PEL supernatants showed reduction of FITC-dextran uptake, reduction of MLR allostimulatory activity and altered expression of surface molecules, suggesting that cytokines released by PEL adversely affect DC differentiation. (C) 2008 Elsevier B.V. All rights reserved
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