Microarrays detect virus–host interaction
HCV is a small RNA virus that is associated with chronic liver inflammation, fibrosis and formation of liver tumours. The virus replicates within cells by interacting with host membranes possibly through non-structural proteins. However, the precise mechanism of assembly and maintenance of the RNA replication complex are largely unknown. Scientists on the EU-funded 'Mapping of Hepatitis C virus NS4B protein interactions with its host network' (HCV PATHOLOGY) project believed that mapping their interaction with the host proteins should shed light into the viral life cycle. Additionally, it would identify molecular targets with potential therapeutic utilisation. To overcome existing technical limitations to studying viral protein interactions in host cells, the HCV PATHOLOGY team established a microfluidic-based protein array. The platform combined microarrays with in vitro protein expression from a synthetic gene library containing over 13 000 synthetic genes. A total of 10 000 human proteins were imprinted on the chip and served as targets for binding assays with viral proteins. Using this system, scientists identified novel binding partners of the HCV NS3 protease. This has therapeutic ramifications since blocking proteases is one of the established routes for viral therapeutics. Through several scientific collaborations, the HCV PATHOLOGY microfluidic platform could be used to characterise other virus protein interactions or provide answers to key biological questions.
Keywords
Hepatitis C virus, antiviral, protein interactions, NS3 protease, microfluidic platform