Abstract
BackgroundThe Human Immunodeficiency Virus type one (HIV-1) is the major causing pathogen of the Acquired Immune Deficiency Syndrome (AIDS). A large number of HIV-1-related studies are based on three non-human model animals: chimpanzee, rhesus macaque, and mouse. However, the differences in host-HIV-1 interactions between human and these model organisms have remained unexplored.DescriptionHere we present CAPIH (Comparative Analysis of Protein Interactions for HIV-1), the first web-based interface to provide comparative information between human and the three model organisms in the context of host-HIV-1 protein interactions. CAPIH identifies genetic changes that occur in HIV-1-interacting host proteins. In a total of 1,370 orthologous protein sets, CAPIH identifies ~86,000 amino acid substitutions, ~21,000 insertions/deletions, and ~33,000 potential post-translational modifications that occur only in one of the four compared species. CAPIH also provides an interactive interface to display the host-HIV-1 protein interaction networks, the presence/absence of orthologous proteins in the model organisms in the networks, the genetic changes that occur in the protein nodes, and the functional domains and potential protein interaction hot sites that may be affected by the genetic changes. The CAPIH interface is freely accessible at http://bioinfo-dbb.nhri.org.tw/capih.ConclusionCAPIH exemplifies that large divergences exist in disease-associated proteins between human and the model animals. Since all of the newly developed medications must be tested in model animals before entering clinical trials, it is advisable that comparative analyses be performed to ensure proper translations of animal-based studies. In the case of AIDS, the host-HIV-1 protein interactions apparently have differed to a great extent among the compared species. An integrated protein network comparison among the four species will probably shed new lights on AIDS studies.
Highlights
The Human Immunodeficiency Virus type one (HIV-1) is the major causing pathogen of the Acquired Immune Deficiency Syndrome (AIDS)
CAPIH exemplifies that large divergences exist in disease-associated proteins between human and the model animals
Since all of the newly developed medications must be tested in model animals before entering clinical trials, it is advisable that comparative analyses be performed to ensure proper translations of animal-based studies
Summary
The CAPIH interface is unique because it is the first webbased tool to provide comparative information of genetic changes and PTMs in host-pathogen interactions. Comparative analyses of host-HIV interactions may shed some light on the mechanisms of differences in AIDS progression between human and chimpanzee. PTMs, perhaps one of the most important regulatory mechanisms of host-pathogen protein interactions, have been rarely studied in a comparative way. This interface may provide clues to the potential roles of PTMs in HIV infections, and serve as a starting point for studies on host-HIV protein interaction networks in different hosts. FCC, FKL and TJC drafted the manuscript.
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