Projects / Programmes
The role of the PML protein in the antiviral immune response
| Code |
Science |
Field |
Subfield |
| 3.01.00 |
Medical sciences |
Microbiology and immunology |
|
| Code |
Science |
Field |
| B500 |
Biomedical sciences |
Immunology, serology, transplantation |
PML protein, immune response, MHC gene cluster, viral infections, interferon alpha
Researchers (1)
| no. |
Code |
Name and surname |
Research area |
Role |
Period |
No. of publicationsNo. of publications |
| 1. |
22361 |
PhD Martina Bergant Marušič |
Biochemistry and molecular biology |
Head |
2008 - 2010 |
107 |
Organisations (1)
| no. |
Code |
Research organisation |
City |
Registration number |
No. of publicationsNo. of publications |
| 1. |
1540 |
University of Nova Gorica |
Nova Gorica |
5920884000 |
14,067 |
Abstract
PML protein is a defining constituent of nuclear domains 10 (ND10s). ND10s are poorly understood nuclear entities which are involved in apoptosis, tumour growth suppression, senescence and transcriptional regulation. Many DNA and RNA viruses have been reported to alter ND10 composition or even cause their disruption. Type I interferons (IFNs), including anti-viral IFN- α, induce up-regulation of PML protein, which in turn suppresses propagation of certain viruses at an early stage of infection. Recent studies suggest that PML might play a role in the regulation of MHC class I antigen presentation and, consequently, in the host immune response toward viruses and tumour cells. Implication in the reorganisation of the MHC class I gene locus indicates that there must be a connection between PML protein and MHC class I antigen presentation pathway. However, there is still no consensus obtained on the exact role of PML in antigen presentation processes. The main goal of this postdoctoral research is to determine whether virus-induced reorganisation of ND10 domains affects host immune response to viral peptides. First, DNA microarray testing will be performed to elucidate the role of PML protein and its particular isoforms on the expression profile of MHC I and II genes, which are in the first place responsible for antigen presentation. Expression profiling will be supplemented with functional testing of immune response in vitro, where we will investigate the role of PML protein on the MHC class I presentation of selected viral proteins on the cell surface. A process that is inevitable for an effective cytotoxic T-cell response against virus-infected cell as well as tumour cells. PML-related effect of IFN- α on antigen presentation will be also evaluated in order to characterise its activity as therapeutical agent. Better understanding of processes affecting viral-antigen presentation could improve the existing treatment of viral infections and also cancer, because tumour antigens are processed and presented in a very similar way. Deficient antigen presentation is a very serious obstacle for detection and elimination of a virus infection or cancer disease in the processes of host immune response, as well as for the application of adoptive immunotherapy.
Significance for science
Irregularities in the immune response are critically involved in the pathogenesis of numerous diseases of modern time. Although recent studies show that similar mechanism exist also in tumour cells, PML-related regulation of anti-viral response remains largely unknown. Characterization of PML as an important player in processing and presentation of viral and tumour antigens could benefit the treatment and prophylaxis of these diseases.
Our research shows that different viral proteins target PML in a very precise way. We provided evidence that L2 induces a reorganization of PML protein that is human papillomavirus (HPV) type-specific. L2 proteins from low risk (HPV 11) and high-risk (HPV 16) HPV types each target different PML isoforms. We demonstrate for the first time that there are differences in PML targeting even among the same virus type. In addition, we identified in characterized post-translation modification of HPV L2 proteins by SUMO proteins and its affect on the host PML protein, which was not known until now. The differences among HPV types were found also in this case. The mechanisms of viral and host protein regulation found in this study might reflects also in the different outcomes of a virus infection.
Results of the study provide an additional insight into the biology of HPV, which are commonly present in the human population and are of high importance for human health. In addition, new mechanisms of the anti-viral immune response regulation by viral and host proteins were suggested.
Significance for the country
Experimental results regarding interaction of viral proteins and host PML proteins have improved the existing knowledge about the mechanisms of viral infections. In the first place, these results contribute to the better understanding of the HPV viral life cycle in of the interactions between viral in host cell during a viral infection.
The obtained data could later on contribute to the improvement of existing treatment of viral infections and virus-related cancer diseases as well for establishing new therapeutic and prophylactic procedures. We could foresee the direct impact of these results for Slovenian economy and society in the field of general health care and in development of new, innovative therapeuticals and therapies.
Most important scientific results
Annual report
2008,
final report,
final report,
complete report on dLib.si
Most important socioeconomically and culturally relevant results
Annual report
2008,
final report,
final report,
complete report on dLib.si
