Abstract
BackgroundIn order to replicate, HIV, like all viruses, needs to invade a host cell and hijack it for its own use, a process that involves multiple protein interactions between virus and host. The HIV-1, Human Protein Interaction Database available at NCBI's website captures this information from the primary literature, containing over 2,500 unique interactions. We investigate the general properties and biological context of these interactions and, thus, explore the molecular specificity of the HIV-host perturbation. In particular, we investigate (i) whether HIV preferentially interacts with highly connected and 'central' proteins, (ii) known phenotypic properties of host proteins inferred from essentiality and disease-association data, and (iii) biological context (molecular function, processes and location) of the host proteins to identify attributes most strongly associated with specific HIV interactions.ResultsAfter correcting for ascertainment bias in the literature, we demonstrate a significantly greater propensity for HIV to interact with highly connected and central host proteins. Unexpectedly, we find there are no associations between HIV interaction and inferred essentiality. Similarly, we find a tendency for HIV not to interact with proteins encoded by genes associated with disease. Crucially, we find that functional categories over-represented in HIV-host interactions are innately enriched for highly connected and central proteins in the host system.ConclusionsOur results imply that HIV's propensity to interact with highly connected and central proteins is a consequence of interactions with particular cellular functions, rather than being a direct effect of network topological properties. The lack of a propensity for interactions with phenotypically essential proteins suggests a selective pressure to minimise virulence in retroviral evolution. Thus, the specificity of HIV-host interactions is complex, and only superficially explained by network properties.
Highlights
In order to replicate, HIV, like all viruses, needs to invade a host cell and hijack it for its own use, a process that involves multiple protein interactions between virus and host
In order to test the hypothesis that the specificity of HIV interactions is in some way explained by network properties, we examine their biological context by integrating known phenotypic properties
Correcting for ascertainment bias, we find that there is no significant relationship between HIV interaction and protein essentiality, and there is a potential under-representation of disease-association amongst HIV interacting human proteins
Summary
HIV, like all viruses, needs to invade a host cell and hijack it for its own use, a process that involves multiple protein interactions between virus and host. We investigate the general properties and biological context of these interactions and, explore the molecular specificity of the HIV-host perturbation. We investigate (i) whether HIV preferentially interacts with highly connected and 'central' proteins, (ii) known phenotypic properties of host proteins inferred from essentiality and disease-association data, and (iii) biological context (molecular function, processes and location) of the host proteins to identify attributes most strongly associated with specific HIV interactions. Pathogens appear to preferentially interact with "key" human proteins that already participate in multiple interactions and/or have central importance in intra-cellular communication. It has been inferred that this non-uniform contact with the host system represents evolutionary pressure to optimise exploitation of the host cell [8]
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