Medicine and Public Health

Winner: Kameelah Abdullah, University of California, Irvine
Natural Genetic Polymorphism in the NS3 Protein of the Hepatitis C Virus

Hepatitis C Virus (HCV) represents a major public health risk worldwide.After acute infection the majority of infected individuals develop Chronic HCV.It is unknown why some individuals show limited disease progression while others develop severe liver damage and cirrhosis.Differential viral evolution enabling evasion of the host immune system is regarded as a main factor.Many studies link genetic variations in viral epitopes with escape mutation and immune evasion.However, HCV is variable and the role of genotype and subtype specific polymorphisms has not been explored.Our hypothesis is that not all viral variations classified in previous studies are immune escape mutants, but some are subtype specific polymorphisms. We compare all CD8+ and CD4+ epitopes of the NS3 viral gene from over 10 different subtypes in the Los Alamos and European HCV databases. Genome alignment and analysis is done with BioEdit software.We are also doing high throughput sequencing of HCV NS3 gene in viral isolates from chronically infected patients to detect escape mutation/polymorphism ratios.Sequencing data is assembled with the Staden Package and aligned to reference sequences using BioEdit.Preliminary data suggests that there are many subtype specific polymorphisms previously regarded as viral escape mutations in other studies. This new data is useful to identify effective and beneficial epitope specific therapies needed to control HCV replication along with understanding host/viral interactions.