Mapping innate immune host and viral gene interactions in monocytes/macrophages, in particular for IL1b and the LTR region of HIV-1

Abstract

Viruses exploit the host cellrs own cellular machinery to propagate their existence. The macrophage is a key host cell that is invaded by the virus and it serves as a sentinel and pivotal mediator of the innate immune response. The idea that molecular mimicry is involved in innate immunity and plays a role in human disease has been previously proposed. However, the precise mechanism by which viral and host genes are regulated and whether there is evidence for molecular mimicry by the viral gene has not been well characterized. Here we show that the viral and host genes are regulated by a complex assembly of cellular transcription factors at their respective promoter regions. Through a team-based lresearch synthesisr approach we focused on constructing a systems level understanding of the host-viral interactions during the initial phases of viral infection. The aim was not only to be able to define control and interaction pathways but to also identify potential structural homologies between promoter elements in the interacting host and viral genes. Various avenues of systems biology and bioinformatics were explored, such as biological data-mining, provenance, and curation, in order to gain a comprehensive understanding of biological pathways. Our results demonstrated how networks and systems extracted from ldata-richr high throughput genomic and proteomic studies and from data-mining of scientific literature can be used to elucidate biological pathways that we constructed using in silco approaches. We anticipate our work to be an initial platform from which more sophisticated in vitro and in silico models for investigating host and viral gene interactions may be build. For example, a statistical model could be designed to investigate the probability of mimicry occurring in a biological system. Furthermore, inhibition of one or more of the cellular transcriptional factors used in the regulation of the viral gene promoter can be used as a major target of antiviral drug development.