The Viral Glycoproteins group was founded in 2002 with the aim to apply the methods developed in the Institute for the study of glycoprotein folding, to a more specific but highly challenging field of molecular biology, the viral envelope packing.
Human hepatitis B and C viruses cause infections of the liver. Worldwide about 300 million people are chronically infected with either HBV or HCV. Of these patients, more than 500.000 die annually from complications of liver disease. Most of these cases occur in developing countries resulting in widespread social and economic problems, especially among the poor people. Sadly, Romania has the highest prevalence of HBV/HCV infections among the EU countries (up to 7% of the population).
Current therapies against HBV, based on replication inhibitors and immune system activators, are associated with severe side effects, resulting frequently in early discontinuation of treatment, while the HCV direct acting antivirals of novel generations are very costly and their use is limited to advanced liver disease. In addition, both viruses are prone to development of resistance to antiviral inhibitors, which reduces significantly the efficiency of treatment. Efficient anti- HBV vaccines are available on market; however, up to 10% individuals fail to develop a protective immune response and remain exposed to infection. In the case of HCV, although intensive research is undergoing, no vaccine has been developed yet and 3-4 million of new infections are expected to occur every year.
Our group is focused on i) studying the interaction between HBV/HCV and their host, the human hepatocyte and identifying novel cellular factors and pathways involved in viral assembly and trafficking that could be targeted by antiviral therapies; ii) designing new viral antigens with improved immunogenic properties; iii) producing these antigens at low costs, using complementary expression systems such as plants and insect cells; iV) developing improved assays adapted for highthroughput screening of chemical compounds with antiviral properties; v) educating and training young researchers in the molecular virology field.
Future projects wiill continue to address production of novel HBV/HCV antigens with improved immunogenic properties, in a cost-effective manner and the role of inositides in the HBV/HCV life cycles.
Hepatitis C virus (HCV) is an important human pathogen that infects the liver and establishes chronic infection in the majority of cases, leading to cirrhosis and hepatocellular carcinoma over the course of many years. Despite recent progress, details of the HCV life cycle are still missing, with the HCV assembly process being particularly poorly understood.
Hepatitis B (HBV) and C viruses (HCV) are important human pathogens resulting in more than 500 million people being currently carriers. Sadly, Romania has the highest prevalence of HBV/HCV infections among the EU countries (up to 7% of the population). Chronically infected patients of HBV and HCV are at high risk to develop severe liver diseases, such as fibrosis, cirrhosis, and hepatocellular carcinoma (HCC).
We aim to produce high yields of novel HBV/HCV antigens with superior immunogenic properties in plants and mammalian cells, based on innovative molecular design and establish in premiere an advanced biotechnological platform for production of best vaccine candidates antigens in algae.
Considering the molecular features of the secretory autophagy, on one hand and the enhanced HBV production by degradation-independent autophagy, on the other hand, we hypothesized that HBV employs this peculiar form of autophagy for its own egress. We further proposed that the M protein plays a pivotal role in tilting the equilibrium between viral degradation and secretion towards the latter, due to the presence of the preS2 domain glycan.
HCV is a major cause of chronic hepatitis worldwide. A better understanding of the HCV life cycle is needed to develop new treatments against this virus. A peculiarity of HCV is the crucial role played by both structural and non-structural proteins in the assembly process. Indeed, practically all HCV proteins have been shown to be involved in the virion assembly process. The present project aims to characterize the spatial and temporal relationship between all the viral proteins during viral assembly.
Lactoferrin (Lf), an immunomodulatory glycoprotein was shown to interfere with the life-cycles of many viruses. Our group has rationally designed and characterized the anti-HBV activity of an Lf-derived peptide containing one of the cationic clusters. This project proved the concept that the development of non-toxic, small Lf-derived molecule(s) with a broad-spectrum anti-viral activity may constitute a valuable, cheaper alternative to the current standard of care.
The objectives of this project aim to identify as many as possible cell proteins with a role in processing HBV envelpe proteins and to make a correlation between the HBV cccDNA which is the replicative form of the virus and the expression level of cellular proteins involved in the debradation of the HBV envelope proteins. The results will be confirmed in vivo using human hepatocytes explanted from the patiens chronically infected with HBV.
Degradation of the viral proteins in infected cells is a way to avoid their aberrant accumulation, on one hand, and generate viral peptides, which will be presented at cell surface by the major histocompatibility complex, raising an immune response, on the other hand. In the case of HBV infection, accumulation of mutant viral proteins within the endoplasmic reticulum can result in a particular phenotype, characterised by a ground glass appearance of hepatocytes.