Associations between HIV and Human Pathways Revealed by Protein-Protein Interactions and Correlated Gene Expression Profiles

Kuang-Chi Chen,Chen-Hsiung Chan,Tse-Yi Wang,Vladimir N Uversky

doi:10.1371/journal.pone.0034240

Kuang-Chi Chen, Chen-Hsiung Chan + Show 2 more

Open Access

https://doi.org/10.1371/journal.pone.0034240

Copy DOI

Abstract

BackgroundAIDS is one of the most devastating diseases in human history. Decades of studies have revealed host factors required for HIV infection, indicating that HIV exploits host processes for its own purposes. HIV infection leads to AIDS as well as various comorbidities. The associations between HIV and human pathways and diseases may reveal non-obvious relationships between HIV and non-HIV-defining diseases.Principal FindingsHuman biological pathways were evaluated and statistically compared against the presence of HIV host factor related genes. All of the obtained scores comparing HIV targeted genes and biological pathways were ranked. Different rank results based on overlapping genes, recovered virus-host interactions, co-expressed genes, and common interactions in human protein-protein interaction networks were obtained. Correlations between rankings suggested that these measures yielded diverse rankings. Rank combination of these ranks led to a final ranking of HIV-associated pathways, which revealed that HIV is associated with immune cell-related pathways and several cancer-related pathways. The proposed method is also applicable to the evaluation of associations between other pathogens and human pathways and diseases.ConclusionsOur results suggest that HIV infection shares common molecular mechanisms with certain signaling pathways and cancers. Interference in apoptosis pathways and the long-term suppression of immune system functions by HIV infection might contribute to tumorigenesis. Relationships between HIV infection and human pathways of disease may aid in the identification of common drug targets for viral infections and other diseases.

Highlights

Acquired immunodeficiency syndrome (AIDS) is a devastating disease that has afflicted the human species for decades
Our results suggest that human immunodeficiency virus (HIV) infection shares common molecular mechanisms with certain signaling pathways and cancers
Interference in apoptosis pathways and the long-term suppression of immune system functions by HIV infection might contribute to tumorigenesis

Summary

Introduction

Acquired immunodeficiency syndrome (AIDS) is a devastating disease that has afflicted the human species for decades. AIDS is caused by human immunodeficiency virus (HIV). Similar to other diseases caused by pathogens, various human pathways must be perturbed or even hijacked to serve the purposes of the HIV virus. Hundreds of human host factors have been identified as necessary during viral infection and replication [1,2,3]. Thousands of protein-protein interactions between HIV and human host proteins have been reported in the literature [4]. AIDS is one of the most devastating diseases in human history. Decades of studies have revealed host factors required for HIV infection, indicating that HIV exploits host processes for its own purposes. The associations between HIV and human pathways and diseases may reveal non-obvious relationships between HIV and non-HIV-defining diseases

Methods

Results

Conclusion