Head of the lab:
Dr. Penelope Mavromara, 
Email: penelopm@hol.gr
Tel:  +30-210-6478877

The hepatitis C virus (HCV) is a small hepatotropic RNA virus classified within the Flaviviridae family, hepacivirus genus. The viral genome is a 9.6 kb, single-stranded, positive-sense RNA molecule encoding a single polyprotein of about 3,000 amino acids. Proteolytic processing of the polyprotein by host and viral proteases yields at least 10 mature viral proteins, including the nucleocapsid C protein, the two envelope glycoproteins E1 and E2, and the non-structural p7, NS2, NS3, NS4A, NS4B, NS5A and NS5B proteins. Recently, an additional protein known as core+1, F or ARFP was identified by our laboratory and independently by two other groups in the United States. This protein is encoded by an alternative reading frame within the core coding region but its function remains unknown. The 5’ and 3’ non-coding regions (5’ NCR and 3’ NCR) are highly conserved. The 5’ NCR contains an internal ribosome entry site (IRES) which allows the translation of the polyprotein. HCV exhibits considerable nucleotide sequence heterogeneity throughout the viral genome.  At least six major HCV genotypes and more than hundred subtypes have been identified worldwide. Furthermore, within an infected individual HCV exist as a mixture of highly related but distinct viral RNA sequences known as quasispecies that can rapidly evolve and become drug resistant.
 
HCV infects approximately 3% of the population worldwide, leading to major health problems. In the majority of cases (85%), HCV infection will progress to chronic, persistent infection that is often associated with liver cirrhosis that can lead to liver failure or hepatocellular carcinoma with fatal outcome. Currently no vaccine or broadly effective therapy is available.
 
It is now well established that HCV uses a complex mechanism to evade or subvert innate and adaptive immune responses and to establish persistent infection. To this end, the study of the function of individual viral proteins remains a promising area of research as it is expected to shed light into our understanding of the mechanisms of viral pathogenesis and antiviral resistance.
 
The research in our laboratory is mainly focused on the functional analysis of the HCV genome and the development of novel therapeutics using modern molecular and cellular approaches. Our group was one of the first three groups which independently discovered a novel protein for HCV, namely ARFP, F or core+1 and we are currently interested to elucidate  the mechanisms for CORE+1 expression and its role in viral pathogenesis.

1. To study the functional properties of selected HCV proteins including core/core+1, NS4B, NS5A.
2. To develop novel strategies and reagents to control HCV infection including new generation of HCV vaccines based on the use of novel viral-based gene delivery systems.
3. To elucidate the molecular mechanisms implicated in the translation of the HCV genome
4. To assess the effect of genetic heterogeneity in the functional properties of HCV proteins, including core+1.
5. To develop novel immunodiagnostic tools for HCV detection.