Dissecting the HIV-specific immune response: a systems biology approach

Abstract

Purpose of review: Several unique HIV-infected or HIV-resistant cohorts have been studied over the years to try and delineate the correlates of protection. Although several mechanisms have been put forward, studies aiming to integrate the different mechanisms into a comprehensive model are still lacking. Current systems biology approaches emphasize the importance of unifying independent datasets, provide tools that facilitate hypothesis formulation and testing, and direct us toward uncovering novel therapeutic targets by defining molecular networks perturbed during disease. This review will focus on the current findings that utilized systems biology techniques in order to identify correlates of protection from HIV disease progression and resistance to infection in unique cohorts of individuals as well as in nonhuman primate models of SIV infection.

Recent findings: Using systems biology technologies and data analysis tools, the studies described herein have found that pathways implicated in survival, cell cycling, inflammation, and oxidative stress work in unison to limit pathology caused by chronic immune activation. This situation favors the survival of effector lymphocytes and limits the dissemination of viral particles in HIV elite controllers, exposed-uninfected individuals, and natural hosts of SIV infection.

Summary: Systems and computational biology tools have clearly expanded our understanding of HIV pathogenesis by unifying independent observations and by giving us novel molecular targets to pursue. These molecular signatures have the potential to uncover correlates of protection in HIV disease and, in the era of personalized medicine, to determine predictive signatures of treatment efficacy and/or failure.

FIGURE 1

Network of proteins involved in the heat shock response, regulation of inflammation, apoptosis, and protein folding. Connectivity is based on analysis using the Ingenuity Biological Database. Gray lines indicate different gene interactions and dotted lines indicate indirect interactions. Bold black lines ending with the – symbol indicate inhibition. The coloring of the nodes is based on the fold change between elite controllers and chronically infected patients, with green colors indicating upregulated genes in HIV-specific CD8 T cells isolated from elite controllers.