Viral Glycoproteins

Viral Glycoproteins Department

Viral Glycoproteins

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.

Norica Nichita, Dr.
Norica Nichita, Dr.

Head of Department, Deputy Director

Dr. Nichita received her PhD at the Institute of Biochemistry in 2000, working on the role of N-glycosylation on protein folding. This study was performed in close collaboration with the University of Oxford, where she spent 3 months/year working in the Department of Biochemistry (1997-2000, as a beneficiary of a NATO fellowship). Dr. Nichita has shown for the first time the strict dependence of a cellular protein, tyrosinase, on the presence of N-linked glycans for native folding and biological activity. Following the award of a Royal Society Fellowship, Dr. Norica Nichita started her post-doctoral studies at the University of Oxford in 2000. Using her co More...

Catalin Lazar, PhD
Catalin Lazar, PhD

Scientific Researcher II

Catalin Lazar is a researcher in the Institute of Biochemistry of the Romanian Academy. Catalin is currently working in Viral Glycoproteins in the Viral Glycoproteins.

Costin-Ioan Popescu, PhD
Costin-Ioan Popescu, PhD

Scientific Researcher II

Dr. Costin-Ioan Popescu is leading the Hepatitis C Virus group in the Department of Viral Glycoproteins of the Institute of Biochemistry of the Romanian Academy. Costin-Ioan Popescu defended his PhD thesis at University of More...

Cristina Scurtu
Cristina Scurtu

Research Assistant

Cristina Scurtu is a researcher in the Institute of Biochemistry of the Romanian Academy. Cristina is currently working in Viral Glycoproteins in the Viral Glycoproteins.

Lia Cucos, Ms.
Lia Cucos, Ms.

PhD Student

Graduated with a MSc in Synthetic Biology at Newcastle University and with a BSc in Experimental Biology from the University of Bucharest, Faculty of Biology. More...

Mihaela-Olivia Dobrica, PhD
Mihaela-Olivia Dobrica, PhD

Research Assistant

Mihaela-Olivia Dobrica is a researcher in the Institute of Biochemistry of the Romanian Academy. Mihaela-Olivia is currently working in Viral Glycoproteins in the Viral Glycoproteins.

  1. Nedelcu I, Florian P, Ion D, Militaru E, Damalan A, Popescu CI, Hristea ANedelcu I et al . "Dynamics of serum cross-neutralization capacity against SARS-CoV-2 Delta variant in convalescent COVID-19 patients", Journal of medical virology 96(2): e29448, (2024)
    doi: 10.1002/jmv.29448
    IF: 12.70AI: 1.82
  2. Pantazica AM, van Eerde A, Dobrica MO, Caras I, Ionescu I, Costache A, Tucureanu C, HSteen H, Lazar C, Heldal I, Haugslien S, Onu A, Stavaru C, Nichita N, Liu Clarke JPantazica AM et al . "The “humanized” N-glycosylation pathway in CRISPR/Cas9-edited Nicotiana benthamiana significantly enhances the immunogenicity of a S/preS1 Hepatitis B Virus antigen and the virus-neutralizing antibody response in vaccinated mice", Plant Biotechnology Journal, (2023)
    IF: 13.20AI: 2.17
  3. Hang Su, André van Eerde, Espen Rimstad, Ralph Bock, Norica Nichita, Igor A Yakovlev, Jihong Liu ClarkeHang Su et al . "Plant-made vaccines against viral diseases in humans and farm animals", Frontiers in Plant Science(14:1170815), (2023)
    doi: 10.3389/fpls.2023.1170815
    IF: 6.20AI: 1.10
  4. Ng E, Dobrica MO, Harris JM, Wu Y, Tsukuda S, Wing PAC, Piazza P, Balfe P, Matthews PC, Ansari MA, McKeating JANg E et al . "An enrichment protocol and analysis pipeline for long read sequencing of the hepatitis B virus transcriptome", Journal of General Virology 5(104), (2023)
    doi: 10.1099/jgv.0.001856
    IF: 5.10AI: 1.05
  5. Anghel SA, Badea RA, Chiritoiu G, Patriche DS, Alexandru PR, Pena FAnghel SA et al . "Novel luciferase-based GLP-1 reporter assay reveals naturally-occurring secretagogues", British journal of pharmacology, (2022)
    IF: 9.47AI: 1.62
  6. Pantazica A-M, Dobrica MO, Lazar C, Scurtu C, Tucureanu C, Caras I, Ionescu I, Costcahe A, Onu A, Liu Clarke J, Stavaru C, Nichita NPantazica A-M et al . "Efficient cellular and humoral immune response and production of virus-neutralizing antibodies by the Hepatitis B Virus S/preS116-42 antigen", Frontiers in Immunology, (2022)
    IF: 8.78AI: 1.94
  7. Bucataru I, Dragomir I, Asandei A, Pantazica A-M, Ghionescu A, Nichita N, Park Y, Tudor Luchian TBucataru I et al . "Probing the Hepatitis B Virus E-Antigen with a Nanopore Sensor Based on Collisional Events Analysis", Biosensors 596(12): 1-15, (2022)
    IF: 5.74
  8. Popescu MA, Patriche D, Dobrica MO, Pantazica AM, Flintoaca Alexandru PR, Rouillé Y, Popescu CI, Branza-Nichita NPopescu MA et al . "Sac1 phosphatidylinositol 4-phosphate phosphatase is a novel host cell factor regulating Hepatitis B Virus particles assembly and release", The FEBS journal, (2022)
    IF: 5.62
    IF: 1.40
  10. Pantazica AMM, Cucos LM, Stavaru C, Liu Clarke J, Branza-Nichita NPantazica AMM et al . "Challenges and Prospects of Plant-Derived Oral Vaccines against Hepatitis B and C Viruses", Plants 10(10): 1-17, (2021)
    IF: 4.60
  11. Dobrica MO, Lazar C, Nichita N*Dobrica MO et al . "N-Glycosylation and N-Glycan Processing in HBV Biology and Pathogenesis", Cells 6(9), (2020)
    IF: 5.60
  12. Codruta C. Popescu, Marius C. Stoian, Lia-Maria Cucos, Anca G. Coman, Antonio Radoi, Anca Paun, Niculina D. H˘adade, Arnaud Gautier, Costin-Ioan Popescu and Mihaela MatacheCodruta C. Popescu et al . "A polycarboxylic chelating ligand for efficient resin purification of His-tagged proteins expressed in mammalian systems", RSC Advances(10): 23931–23935, (2020)
    IF: 3.04
  13. Dobrica Mihaela-Olivia, Catalin Lazar, Norica NichitaDobrica Mihaela-Olivia et al . "Production of Chimeric Hepatitis B Virus Surface Antigens in Mammalian Cells", Methods in Molecular Biology, Blaine Pfeifer and Andrew Hill (eds.). Springer Science. 2183(Vaccine Delivery Technology: Methods and Protocols), (2020)
  14. Dobrica MO, Lazar C, Paruch L, van Eerde A, Clarke JL, Tucureanu C, Caras I, Ciulean S, Onu A, Tofan V, Branzan A, Urban S, Stavaru C, Branza-Nichita NDobrica MO et al . "Oral administration of a chimeric Hepatitis B Virus S/preS1 antigen produced in lettuce triggers infection neutralizing antibodies in mice", Vaccine 36(38): 5789-5795, (2018)
    IF: 3.27
  15. Uta M, Sima LE, Hoffmann P, Dinca V, Branza-Nichita NUta M et al . "Development of a DsRed-expressing HepaRG cell line for real-time monitoring of hepatocyte-like cell differentiation by fluorescence imaging, with application in screening of novel geometric microstructured cell growth substrates", Biomedical microdevices 19(1): 3, (2017)
    IF: 2.08AI: 0.70
  16. Vlaicu O, Selescu T, Pastrama F, Munteanu C, Riva L, Dubuisson J, Rouille Y, Popescu CIVlaicu O et al . "Novel replicons and trans-encapsidation systems for Hepatitis C Virus proteins live imaging and virus-host interaction proteomics", Journal of virological methods 246: 42-50, (2017)
  17. Clarke JL, Paruch L, Dobrica MO, Caras I, Tucureanu C, Onu A, Ciulean S, Stavaru C, Eerde A, Wang Y, Steen H, Haugslien S, Petrareanu C, Lazar C, Popescu CI, Bock R, Dubuisson J, Branza-Nichita NClarke JL et al . "Lettuce-produced hepatitis C virus E1E2 heterodimer triggers immune responses in mice and antibody production after oral vaccination", Plant biotechnology journal 15(12): 1611-1621, (2017)
  18. Lazar C, Uta M, Petrescu SM, Branza-Nichita NLazar C et al . "Novel function of the endoplasmic reticulum degradation-enhancing α-mannosidase-like proteins in the human hepatitis B virus life cycle, mediated by the middle envelope protein", Cellular microbiology 19(2), (2017)
  19. Lazar C, Macovei A, Petrescu S, Branza-Nichita NLazar C et al . "Activation of ERAD pathway by human hepatitis B virus modulates viral and subviral particle production", PloS one 7(3): e34169, (2012)
    IF: 3.73AI: 1.50
  20. Pollock S, Nichita NB, Böhmer A, Radulescu C, Dwek RA, Zitzmann N.Pollock S et al . "Polyunsaturated liposomes are antiviral against hepatitis B and C viruses and HIV by decreasing cholesterol levels in infected cells", Proc Natl Acad Sci U S A. 104(40): 17176-81, (2008)
    IF: 9.50
Identification of host factors involved in hepatitis C virus assembly and characterization of their potential role in vivo 2014
Project director: Costin-Ioan Popescu

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.

Development of a cost effective Romania-Norway joint plant-based technology platform for production of vaccines against Human Hepatitis viruses B (HBV) and C (HCV) 2014-2017
Project director: Norica Nichita

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).

EEA Grants (2014-2021): Next Generation Viral Hepatitis B and C vaccine development in plants and algae using advanced biotechnological tools; ‘’Dezvoltare de vaccinuri de ultima generatie anti Virusurile Hepatice B si C in plante si alge, utilizand metode biotehnologice avansate’’ 2019-2023
Acronym: SmartVac
Budget: 1.500.000 EUR
Project director: Norica Nichita

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.

Molecular mechanisms of hepatitis B virus egress 2018-2020
Budget: 100.000 Euro
Project director: Catalin Lazar

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.

Real-time imaging of the viral modules during Hepatitis C Virus assembly 2014
Acronym: HCVAsmImage
Project director: Costin-Ioan Popescu

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.

Human lactoferrin-derived peptides with broad spectrum antiviral activity 2017-2018
Budget: 133.300 Euro
Project director: Catalin Lazar

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 role of the endoplasmic reticulum-associated degradation in establishment of persistent Hepatitis B Virus infection 2013-2016
Acronym: HBVERAD
Budget: 174.400 Euro
Project director: Catalin Lazar

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 pathways of human hepatitis B virus envelope proteins 2010-2012
Acronym: -
Budget: 64.500 Euro
Project director: Catalin Lazar

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.