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      Antibodies reacting with JCPyV_VP2 _167-15mer as a novel serological marker for JC polyomavirus infection

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          Abstract

          Background

          JC polyomavirus (JCPyV) is a widespread human polyomavirus that usually resides latently in its host, but can be reactivated under immune-compromised conditions potentially causing Progressive Multifocal Leukoencephalopathy (PML). Detection of antibodies against the major capsid protein VP1 currently is the main marker for assessment of infection with JCPyV.

          Methods

          Based on a peptide microarray, peptide JCPyV_VP2_167-15mer was selected and a peptide ELISA was developed for detection of antibodies directed against this peptide. Epitope mapping and computational modelling was performed to further characterize this peptide. In a cohort of 204 healthy subjects it was investigated whether antibodies against JCPyV_VP2_167-15mer were correlated with VP1 serology or urinary viral load.

          Results

          Epitope mapping of peptide JCPyV_VP2_167-15mer showed that the minimal epitope consisted of L 173PALTSQEI 181 with amino acids P 174, L 176 and E 180 being essential for antibody recognition. Computational analysis was used to predict that this epitope is located at an exposed domain of the VP2 capsid protein, readily accessible for immune recognition upon infection. No correlation could be observed with JCPyV VP1 antibody levels, or urinary viral load.

          Conclusion

          This work indicates that specific antibodies against JCPyV_VP2_167-15mer might be considered as a novel serological marker for infection with JCPyV.

          Electronic supplementary material

          The online version of this article (doi:10.1186/1743-422X-11-174) contains supplementary material, which is available to authorized users.

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          Most cited references35

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          High-resolution epitope mapping of hGH-receptor interactions by alanine-scanning mutagenesis.

          A strategy, called alanine-scanning mutagenesis, was used to identify specific side chains in human growth hormone (hGH) that strongly modulate binding to the hGH receptor cloned from human liver. Single alanine mutations (62 in total) were introduced at every residue contained within the three discontinuous segments of hGH (residues 2 to 19, 54 to 74, and 167 to 191) that have been implicated in receptor recognition. The alanine scan revealed a cluster of a dozen large side chains that when mutated to alanine each showed more than a four times lower binding affinity to the hGH receptor. Many of these residues that promote binding to the hGH receptor are altered in homologs of hGH (such as placental lactogens and prolactins) that do not bind tightly to the hGH receptor. The overall folding of these mutant proteins was indistinguishable from that of the wild-type hGH, as determined by strong cross-reactivities with seven different conformationally sensitive monoclonal antibodies. The alanine scan also identified at least one side chain, Glu174, that hindered binding because when it was mutated to alanine the receptor affinity increased by more than a factor of four.
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            Cultivation of papova-like virus from human brain with progressive multifocal leucoencephalopathy.

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              Mobyle: a new full web bioinformatics framework

              Motivation: For the biologist, running bioinformatics analyses involves a time-consuming management of data and tools. Users need support to organize their work, retrieve parameters and reproduce their analyses. They also need to be able to combine their analytic tools using a safe data flow software mechanism. Finally, given that scientific tools can be difficult to install, it is particularly helpful for biologists to be able to use these tools through a web user interface. However, providing a web interface for a set of tools raises the problem that a single web portal cannot offer all the existing and possible services: it is the user, again, who has to cope with data copy among a number of different services. A framework enabling portal administrators to build a network of cooperating services would therefore clearly be beneficial. Results: We have designed a system, Mobyle, to provide a flexible and usable Web environment for defining and running bioinformatics analyses. It embeds simple yet powerful data management features that allow the user to reproduce analyses and to combine tools using a hierarchical typing system. Mobyle offers invocation of services distributed over remote Mobyle servers, thus enabling a federated network of curated bioinformatics portals without the user having to learn complex concepts or to install sophisticated software. While being focused on the end user, the Mobyle system also addresses the need, for the bioinfomatician, to automate remote services execution: PlayMOBY is a companion tool that automates the publication of BioMOBY web services, using Mobyle program definitions. Availability: The Mobyle system is distributed under the terms of the GNU GPLv2 on the project web site (http://bioweb2.pasteur.fr/projects/mobyle/). It is already deployed on three servers: http://mobyle.pasteur.fr, http://mobyle.rpbs.univ-paris-diderot.fr and http://lipm-bioinfo.toulouse.inra.fr/Mobyle. The PlayMOBY companion is distributed under the terms of the CeCILL license, and is available at http://lipm-bioinfo.toulouse.inra.fr/biomoby/PlayMOBY/. Contact: mobyle-support@pasteur.fr; mobyle-support@rpbs.univ-paris-diderot.fr; letondal@pasteur.fr Supplementary information: Supplementary data are available at Bioinformatics online.
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                Author and article information

                Contributors
                olagatie@its.jnj.com
                tvanloy@its.jnj.com
                ltritsm1@its.jnj.com
                lstuyver@its.jnj.com
                Journal
                Virol J
                Virol. J
                Virology Journal
                BioMed Central (London )
                1743-422X
                1 October 2014
                1 October 2014
                2014
                : 11
                : 1
                : 174
                Affiliations
                [ ]Janssen Diagnostics, Turnhoutseweg 30, 2340 Beerse, Belgium
                [ ]Janssen Research and Development, Turnhoutseweg 30, 2340 Beerse, Belgium
                Article
                2502
                10.1186/1743-422X-11-174
                4194363
                25273879
                b0f32e99-64df-43f7-8e76-03fafd44e8ee
                © Lagatie et al.; licensee BioMed Central Ltd. 2014

                This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 26 June 2014
                : 27 September 2014
                Categories
                Research
                Custom metadata
                © The Author(s) 2014

                Microbiology & Virology
                jc polyomavirus,biomarker,peptide serology,vp2,progressive multifocal leukoencephalopathy

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