Cataloguing the HIV type 1 human protein interaction network

Abstract

Although many interactions between HIV-1 and human proteins have been reported in the scientific literature, no publicly accessible source for efficiently reviewing this information was available. Therefore, a project was initiated in an attempt to catalogue all published interactions between HIV-1 and human proteins. HIV-related articles in PubMed were used to develop a database containing names, Entrez GeneIDs, and RefSeq protein accession numbers of interacting proteins. Furthermore, brief descriptions of the interactions, PubMed identification numbers of articles describing the interactions, and keywords for searching the interactions were incorporated. Over 100,000 articles were reviewed, resulting in the identification of 1448 human proteins that interact with HIV-1 comprising 2589 unique HIV-1-to-human protein interactions. Preliminary analysis of the extracted data indicates 32% were direct physical interactions (e.g., binding) and 68% were indirect interactions (e.g., upregulation through activation of signaling pathways). Interestingly, 37% of human proteins in the database were found to interact with more than one HIV-1 protein. For example, the signaling protein mitogen-activated protein kinase 1 has a surprising range of interactions with 10 different HIV-1 proteins. Moreover, large numbers of interactions were published for the HIV-1 regulatory protein Tat and envelope proteins: 30% and 33% of total interactions identified, respectively. The database is accessible at http://www.ncbi.nlm.nih.gov/RefSeq/HIVInteractions/ and is cross-linked to other National Center for Biotechnology Information databases and programs via Entrez Gene. This database represents a unique and continuously updated scientific resource for understanding HIV-1 replication and pathogenesis to assist in accelerating the development of effective therapeutic and vaccine interventions.

FIG. 1.

Visualization of the HIV-1 human protein interaction network. The network was visualized with InterView. Gray ovals represent HIV-1 proteins. Colored circles represent human proteins and are shown clustering around the HIV-1 protein they interact with. Human proteins that interact with multiple viral proteins are shown toward the center of the image rather than clustered around a specific HIV-1 protein. Colors correspond to human protein categories based on cellular component Gene Ontology (GO) terms. The number of proteins in each category and percentage of the total 1448 human proteins interacting with HIV-1 are indicated in parentheses. Black lines correspond to direct interactions (e.g., binding) and gray lines to indirect interactions (e.g., downregulation). Circles for specific human proteins of interest discussed in the text (MAPK1, MAPK3, PRKCA, and IFNG) are indicated with dashed red lines. Overlapping circles are a result of the visualization process and do not imply any specific relationship. See supporting online materials for alternative visualizations of the HIV-1 human protein interaction network based on biological process and molecular function GO terms, and for information about specific human proteins that interact with multiple viral proteins.