Abstract

Measuring the altered gene expression level and identifying differentially expressed genes/proteins during HIV infection, replication and latency is fundamental for broadening our understanding of the mechanisms of HIV infection and T-cell dysfunction. Such studies are crucial for developing effective strategies for virus eradication from the body. Inspired by the availability and enrichment of gene expression data during HIV infection, replication and latency, in this study, we proposed a novel compendium termed HIVed (HIV expression database; http://hivlatency.erc.monash.edu/) that harbours comprehensive functional annotations of proteins, whose genes have been shown to be dysregulated during HIV infection, replication and latency using different experimental designs and measurements. We manually curated a variety of third-party databases for structural and functional annotations of the protein entries in HIVed. With the goal of benefiting HIV related research, we collected a number of biological annotations for all the entries in HIVed besides their expression profile, including basic protein information, Gene Ontology terms, secondary structure, HIV-1 interaction and pathway information. We hope this comprehensive protein-centric knowledgebase can bridge the gap between the understanding of differentially expressed genes and the functions of their protein products, facilitating the generation of novel hypotheses and treatment strategies to fight against the HIV pandemic.

Highlights

  • Over 32 million are infected with HIV and with over 2 million new infections every year; it is still a major public health burden (UNAIDS 2010; http://www.unaids.org/globalreport/Global_report.htm)

  • Studying the mechanisms of action of existing LRAs (Latency-Reversing Agents) could shed light on newer therapeutic interventions by comparing host cell expression data from different cellular models and LRAs. Most of these data are hosted on individual websites: Litchi[21], Peachi[28] or in collections[29], which mainly focus on annotating the genome and expression of related genes during HIV infection, replication, and/ or latency, with little information on the functional annotations of their protein products

  • Besides the gene expression profiles mediated by HIV, we investigated whether the deposited entries in HIVed are HIV replication factors

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Summary

Number of proteins with secondary structures

Different experimental settings, such as Litchi[21], Peachi[28] and GuavaH29 These online resources provide useful information regarding the dysregulated human genes and graphical annotations showing the gene expression levels at a single time point and/or during a time course. It is very important to note that none of these databases focuses on the products of the dysregulated genes and their functions Differentiating from these databases, HIVed is featured as a protein-centric knowledgebase with a special focus on the protein product of the dysregulated human genes during HIV infection, replication and latency, by combining and comparing the mainstream gene expression datasets across different experimental protocols. HIVed will enable the virologists and immunologists to map the human genes disturbed (or perturbed) by HIV to their functional annotations and generate hypotheses for HIV cure research

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