Laboratory of Virus Molecular Biology
Previous and current research:
The research of our group is focused on structure of viral proteins and their
function in virus entry, spread and modulation of immune response. Our main
models are alpha-herpesviruses and human hepatitis C (HCV) virus.
Herpesviruses are widespread important human and animal pathogens and it is
estimated that about 80% of human population is chronically infected with at
least two viruses from that family. We study the role of virion glycoproteins in
the first stages of infection and in the transmission of the virus between cells.
To understand the function of viral proteins, we construct live viral mutants with
deleted or modified genes as well as the stable cell lines expressing the genes
of interest. The intramolecular localization and transport of viral proteins in
infected cells is analysed by confocal microscopy. The construction of
recombinant viral particles labeled with GFP allows us to make direct
observations of virus multiplication and spread in live cells. The other area of
interest is the mechanism of “immune evasion”, modulation of host immune
response after infection with herpesviruses.
HCV is a one the most dangerous human pathogens and the methods of its
control are not efficient. There is no available vaccine to prevent HCV infection.
Our group has been involved in several international projects, funded by EU
Framework Programs, aimed at the development of new strategies of HCV
control. Two projects are focused on studies of HCV entry with the goal to
develop new antiviral therapies targeting the early stages of infection. The aim
of the other large project conducted by twelve partners from seven countries, is
to develop efficacious prophylactic and therapeutic vaccines to HCV. Two
candidate vaccines based on adenovirus vectors and recombinant proteins are
tested in pre-clinical and clinical trials.
Selected previous projects:
- Herpesvirus vector vaccines against helminth parasite infections in calves and
sheep (4 FP EU INCO-Copernicus project)
- Recombinant baculovirus expressing pseudorabies virus (PRV) glycoproteins
in mammalian cells as vaccine against PRV infection (EU 5 FP project)
- Analysis of structure and function of ANK proteins of parapox virus
- Bovine herpesvirus 1 : function of envelope glycoproteins gE and gI in viral cell-to-cell spread
- The function of viral proteins Ul49.5 and gM of varicelloviruses in the
interference with MHC class I viral antigens presentation
- Modification of cellular cytoskeleton caused by Us3 protein kinase of BHV-1
- Structure and function of hepatitis C glycoproteins : biochemical and functional characterization of E1E2 from various genotypes, mutagenesis of the E1 E2 glycoproteins and analysis of recombinant proteins.
- Construction and characterization of new adenovectors encoding HCV
Future projects and goals:
Our main goal is the elucidation of various mechanisms of virus–host cell
interaction (virus entry, transmission, modulation of host cell environment) which will help us contribute to the development of novel anti-viral therapies and safe and effective vaccines.
1. Brzozowska A, Rychłowski M, Lipińska A D, Bieńkowska-Szewczyk K. Point
mutations in BHV-1 Us3 gene abolish its ability to induce cytoskeletal changes in various cell types. Veterinary Microbiology 2010; 143(1):8-13.
2. Adamiak B, Trybala E, Mardberg K, Johansson M, Liljeqvist J A, Olofsson S
et al. Human antibodies to herpes simplex virus type 1 glycoprotein C are
neutralizing and target the heparan sulfate-binding domain. Virology 2010; 400
3. Morawska-Onyszczuk M, Bieńkowska-Szewczyk K, Dobbelstein M. Self-
association of adenovirus type 5 E1B-55 kDa as well as p53 is essential for
their mutual interaction. Oncogene 2010; 29(12):1773-1786.
4. Grabowska A K, Lipińska A D, Rohde J, Szewczyk B, Bieńkowska-Szewczyk
K, Rziha H J. New baculovirus recombinants expressing Pseudorabies virus
(PRV) glycoproteins protect mice against lethal challenge infection. Vaccine
5. Koppers-Lalic D, Verweij M C, Lipińska A D, Wang Y, Quinten E, Reits E A
et al. Varicellovirus UL49.5 proteins differentially affect the function of the
transporter associated with antigen processing, TAP. PLoS Pathogens 2008; 4(5).
6. Reszka N, Rijsewijk F A, Zelnik V, Moskwa B, Bienkowska-Szewczyk K.
Haemonchus contortus: Characterization of the baculovirus expressed form of
aminopeptidase H11. Experimental Parasitology 2007; 117(2):208-213.
7. Rychlowska M, Bienkowska-Szewczyk K. Hepatitis C - new developments in
the studies of the viral life cycle. Acta Biochimica Polonica 2007; 54(4):703-715.
8. Lipińska A D, Koppers-Lalic D, Rychlowski M, Admiraal P, Rijsewijk F A,
Bieńkowska-Szewczyk K et al. Bovine herpesvirus 1 UL49.5 protein inhibits the
transporter associated with antigen processing despite complex formation with
glycoprotein M. Journal of Virology 2006; 80(12):5822-5832.
9. Owsianka A M, Timms J M, Tarr A W, Brown R J, Hickling T P, Szwejk A et
al. Identification of conserved residues in the E2 envelope glycoprotein of the
hepatitis C virus that are critical for CD81 binding. Journal of Virology 2006; 80
Head: Prof. Krystyna Bieńkowska-Szewczyk
Agnieszka Brzozowska, Katarzyna Grzyb PhD, Andrea Lipińska PhD, Małgorzata Rychłowska PhD,
Michał Rychłowski PhD,
Alicja Chmielewska, Małgorzata Graul, Weronika Hoffmann, Vasil Krapchev, Dorota Lesiak,
Mirosława Panasiuk, Karolina Zimmer