The HIVToolbox 2 web system integrates sequence, structure, function and mutation analysis

• Published in: PloS one Vol. 9; no. 6; p. e98810
• Main Authors: Sargeant, David P, Deverasetty, Sandeep, Strong, Christy L, Alaniz, Izua J, Bartlett, Alexandria, Brandon, Nicholas R, Brooks, Steven B, Brown, Frederick A, Bufi, Flaviona, Chakarova, Monika, David, Roxanne P, Dobritch, Karlyn M, Guerra, Horacio P, Hedden, Michael W, Kumra, Rma, Levitt, Kelvy S, Mathew, Kiran R, Matti, Ray, Maza, Dorothea Q, Mistry, Sabyasachy, Novakovic, Nemanja, Pomerantz, Austin, Portillo, Josue, Rafalski, Timothy F, Rathnayake, Viraj R, Rezapour, Noura, Songao, Sarah, Tuggle, Sean L, Yousif, Sandy, Dorsky, David I, Schiller, Martin R
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 02.06.2014; Public Library of Science (PLoS)
• Subjects: Amino Acid Sequence; Analysis; Anatomy; Anti-HIV Agents - chemistry; Antigenic determinants; Binding sites; Binding Sites - genetics; Biology and Life Sciences; Business travel; Computer and Information Sciences; Conservation; Conserved sequence; Consolidation; Data mining; Data processing; Databases, Genetic; DNA Mutational Analysis; Drug resistance; Drug Resistance, Viral - genetics; Epitopes; Genetic aspects; Health aspects; HIV; HIV - drug effects; HIV - genetics; HIV - metabolism; HIV infections; Homesteading; Human immunodeficiency virus; Human Immunodeficiency Virus Proteins - chemistry; Human Immunodeficiency Virus Proteins - drug effects; Human Immunodeficiency Virus Proteins - genetics; Human Immunodeficiency Virus Proteins - metabolism; Humans; Hyperlinks; Infections; Interfaces; Internet; Jet lag; Medicine and health sciences; Mutation; Nanoparticles; Pathogenesis; Protease; Proteases; Protection and preservation; Protein Conformation; Protein interaction; Protein Multimerization; Protein Processing, Post-Translational; Protein structure; Protein-protein interactions; Proteinase; Proteins; Sequence Analysis, Protein; Software; Structure-function relationships; Studies; Tat protein; Viruses; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0098810

There is enormous interest in studying HIV pathogenesis for improving the treatment of patients with HIV infection. HIV infection has become one of the best-studied systems for understanding how a virus can hijack a cell. To help facilitate discovery, we previously built HIVToolbox, a web system for visual data mining. The original HIVToolbox integrated information for HIV protein sequence, structure, functional sites, and sequence conservation. This web system has been used for almost 40,000 searches. We report improvements to HIVToolbox including new functions and workflows, data updates, and updates for ease of use. HIVToolbox2, is an improvement over HIVToolbox with new functions. HIVToolbox2 has new functionalities focused on HIV pathogenesis including drug-binding sites, drug-resistance mutations, and immune epitopes. The integrated, interactive view enables visual mining to generate hypotheses that are not readily revealed by other approaches. Most HIV proteins form multimers, and there are posttranslational modification and protein-protein interaction sites at many of these multimerization interfaces. Analysis of protease drug binding sites reveals an anatomy of drug resistance with different types of drug-resistance mutations regionally localized on the surface of protease. Some of these drug-resistance mutations have a high prevalence in specific HIV-1 M subtypes. Finally, consolidation of Tat functional sites reveals a hotspot region where there appear to be 30 interactions or posttranslational modifications. A cursory analysis with HIVToolbox2 has helped to identify several global patterns for HIV proteins. An initial analysis with this tool identifies homomultimerization of almost all HIV proteins, functional sites that overlap with multimerization sites, a global drug resistance anatomy for HIV protease, and specific distributions of some DRMs in specific HIV M subtypes. HIVToolbox2 is an open-access web application available at [http://hivtoolbox2.bio-toolkit.com].