Modelling of Adaptive and Innate Immune Responses and Identification of Crosstalk Amongst Various Signaling Pathways Involved in HCV Infection Using Systems Biology Approach
The interactive network of host immune system mounts an antiviral response against Hepatitis C Virus (HCV) and thus forms the first line of host defense against the viral infection. However, chronic HCV infection may result when the host immune system fails to clear the infection efficiently. There are various host and viral factors which contribute to failure of host defense system. In this regard, the virus has evolved escape strategies at various host defense levels which hinders viral clearance from the body. It is believed that virus elimination is linked to the direct outcome of the interactions between the various innate and adaptive immune pathways and HCV proteins. Yet the exact hubs of cross-talks amongst the innate and adaptive immune system is still not clearly understood. The vast array of data has been generated over the years through conventional wet lab approaches. However, obtaining an integrated view of the complex immune response network while exploring the qualitative aspects of the crosstalk amongst the innate and adaptive immune responses presents an enormous challenge for the biologists. In order to understand the collective functioning of immune response system during HCV infection, a study was designed based on systems biology approaches and computational biology techniques. Systems biology approaches enable to analyze highly complex large networks and gives a holistic view of the whole system under study. Computational approach of Petri nets was applied to model and simulate the immune response network in the presence of HCV, utilizing the available experimental data from literature. The study focused on the development of an integrated immune response network consisting only the important pathways of both innate and adaptive signaling pathways. It highlighted the important junctions of innate and adaptive immune systems crosstalk. The model presents a simplified formalization of the HCV related immune responses which improved our understanding of continuous dynamics of infection, identification of crucial parameters and suggested directions for further experimental research.
Keywords - HCV, systems biology, Petri net, HCV model, HCV core, HCV Envelope 2,