Abstract

BackgroundMany HIV databases and applications focus on a limited domain of HIV knowledge. Since even a “simple” organism like HIV represents a very complex system with many interacting elements, the fractured structure of existing databases and applications likely limits our ability to investigate and understand HIV. To facilitate research, therefore, we have built HIVToolbox, which integrates much of the knowledge about HIV proteins and presents the data in an interactive web application. HIVToolbox allows quick and convenient hypotheses generation, experiment interpretation, and potential new drug structure creation.MethodsHIVToolbox was built as a standard three-tier J2EE web application, consisting of 1) an underlying relational MySQL database, 2) a set of standard Java data access objects that pull data from the database, and 3) a set of dynamic web pages the user interacts with. HIV-1 data from external sources such as the Protein Data Bank, NCBI, Los Alamos, etc. was collected, curated, and stored in the HIVToolbox database. Additional data, such as homology and position statistics matrices, was generated from existing data. Since version 1, drug binding site and drug resistant mutation data has also been added.ResultsHIVToolbox was used to create several new hypotheses about HIV-1 integrase, including predicting the location of a CK2 phosphorylation site, which was later confirmed by experiment. A new version of HIVToolbox support display of the 3D locations of drug resistant mutations on surface plots of HIV proteins and the drug binding sites for structures of complexes of HIV proteins with drugs.ConclusionHIVToolbox is an open-access web application that allows virologists and structural biologists to access detailed information about HIV-1 proteins, such as sequence, structure, functional sites and relationships, homology, drug binding sites, and drug resistant mutations, and to immediately see the relationships between any or all of them. Weblink: [http://hivtoolbox.bio-toolkit.com]

Highlights

  • Many human immunodeficiency virus (HIV) databases and applications focus on a limited domain of HIV knowledge

  • In contrast to what we previously determined for CD8 T cells transduced with the wild type A2-SL9 specific T cell receptors (TCRs), we observed that the A2-YV9 specific T cells could respond in a polyfunctional manner by simultaneously producing tumor necrosis factor alpha (TNF-a), IFN-g, IL-2, and MIP1-b when presented with a wide range of peptide concentrations

  • We investigated the effects of 13 single nucleotide polymorphisms (SNPs) in the ZNRD1 region on human immunodeficiency virus type 1 (HIV-1) infection and progression in five U.S-based treatment-naive HIV-1 longitudinal cohorts consisting of homosexuals, hemophiliacs and injection drug users (IDUs) (n 01028)

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Summary

Introduction

Many HIV databases and applications focus on a limited domain of HIV knowledge. Since even a ‘‘simple’’ organism like HIV represents a very complex system with many interacting elements, the fractured structure of existing databases and applications likely limits our ability to investigate and understand HIV. Results: Up to 3% percent of human cells in spleen, peripheral blood, and thymus/liver implants in HIV-infected BLT mice harbored latent HIV This virus was integrated, activation-inducible, and replication competent. Methods: Analysis of peripheral HIV-1 reservoirs was performed on banked samples (1 pre- and 3 post-RIC-AlloSCT) for both patients, including: 1) quantification of HIV-1 DNA from peripheral blood mononuclear cells (PBMCs), 2) quantification of 2-LTR circles from PBMC episomal DNA, 3) full-length envelope amplification and phenotypic coreceptor usage prediction from proviral DNA, 4) quantification of plasma viremia by a single-copy assay, 5) flow cytometric characterization of lymphocyte subsets and coreceptor expression, and 6) CCR5 genotyping. The evaluation shows that DBS can be a feasible and reliable method for virological monitoring of patients on ARVs in rural areas with transport facilities for referring samples to a central laboratory

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