(2020-2022) – Principal Investigator Anca Botezatu, PhD.
Aim: The aims of the proposal are as follow:
• To identify ND10 components involved in chromatin remodeling (HDAC complexes) and histone chaperones during early viral infection using as experimental models infected human cell lines with HPV16/18 pseudovirions;
• To establish if ND10 complex has a role in intrinsic immune response in hrHPV infection;
• To ascertain the role of histone H3.3 in viral chromatin status during first stages of infection (HPV and ND10 co-localization);
• To understand which viral factors may play a role in regulation of ND10 chromatin remodelers, which may help the virus escape from intrinsic immunity mechanism.
Partners: Coordinator:– „Stefan S. Nicolau” Institute of Virology, project director Anca Botezatu, PhD
Working team: Botezatu A, Plesa A, Iancu I, Fudulu A, Albulescu A
Funding: 431 900 LEI
Project: Research projects to stimulate the establishment of young independent research teams – TE UEFISCDI, PN-III-P1-1.1-TE-2019-1759
Implementation period: september 2020 – august 2022
Summary: Human papilloma viruses (HPVs) are non-enveloped double-stranded DNA genome viruses, divided according to oncogenic potential into low-risk (lrHPV) and high-risk (hrHPV) genotypes for which persistent infection is associated with cervical dysplasia and carcinogenesis. HPVs developed strategies to interfere with innate immune responses, to delay adaptive immune responses and thus to promote oncogenesis. Even if the HPV viral life cycle has been extensively studied, the regulatory proteins that influence viral chromatin and interactions of the viral DNA with complex nuclear structure in the infected cells are still under investigation. The proposal intends to unveil the mechanism of how hrHPV optimizes its own transcription in order to evade the intrinsic immune response being prone to use epigenetic mechanisms to regulate biological activities during virus life cycle. In this context, we hypothesize an association between HPV genome and chromatin remodeling complexes interaction that influences the early viral gene transcription. In order to highlight this we propose the following specific objectives: identifying ND10 components involved in chromatin remodeling complexes and histone chaperones during early viral infection using as experimental models infected human cell lines with HPV16/18 pseudovirions; establishing if ND10 complex has a role in intrinsic immune response in hrHPV infection; discovering the role of histone H3.3 in viral chromatin status during first stages of infection (HPV and ND10 co-localization); understanding which viral factors may play a role in regulation of ND10 chromatin remodelers, which may help the virus escape from intrinsic immunity mechanism. The obtained data will enrich the knowledge in the field of molecular biology and epigenetics of the HPV infection, which may represent a future challenge for developing new therapeutic targets and strategies in disease management. This may open new research direction for HPV–induced tumorigenes
Results:
- Botezatu A, Fudulu A, Iancu IV, Bostan M, Mihaila M, Albulescu A, Diaconu CC, Anton G, Plesa A. Assessment of HPV16 viral oncogenes’ role in genome-wide pattern deposition of MBD2/3 components of NuRD nucleosome remodeling complex. The biochemistrity global summit” 25th IUBMB, 46th FEBS and 15th PABMB Congress, 2022, Lisabona, Portugalia, in FEBS Open Bio 12 (Suppl. S1) (2022), pg 164, P-02.1-024. doi:10.1002/2211-5463.13440, ISSN:2211-5463 IF= 2.792
- Fudulu A, Botezatu A, Albulescu A, Iancu IV, Plesa A, Anton G. The influence of inhibitors targeting epigenetic factors in cervical cancer in vitro model. The biochemistrity global summit” 25th IUBMB, 46th FEBS and 15th PABMB Congress, 2022, Lisabona, Portugalia, in FEBS Open Bio 12 (Suppl. S1) (2022), pg 104, P-01.1-102. doi:10.1002/2211-5463.13440, ISSN:2211-5463 IF= 2.792
- Iancu IV, Botezatu A, Fudulu A, Albulescu A, Huica I, Plesa A. The interplay between long non-coding RNAs expression and DNA methylation in hypoxia. The biochemistrity global summit” 25th IUBMB, 46th FEBS and 15th PABMB Congress, 2022, Lisabona, Portugalia, in FEBS Open Bio 12 (Suppl. S1) (2022), pg 284, P-04.4-041. doi:10.1002/2211-5463.13440, ISSN:2211-5463 IF= 2.792
- Botezatu A, Pleșa A, Iancu IV, Bostan M, Mihaila M, Albulescu A, Fudulu A, Diaconu CC, Anton G. E6 and E7 HPV16 oncogenes influence gene transcription trough the genome-wide pattern deposition of MBD2/3 components of NuRD nucleosome remodeling complex. ESHG 2021- European Human Genetics Virtual Conference, august 28-31, 2021, Session P20 – European Journal of Human Genetics, 30(suppl 1) pg 542-542 P20.004.C. 2022. ISSN:1018-4813, eISSN:1476-5438. IF= 5.351
- Albulescu A, Plesa A, Fudulu A, Iancu IV, Anton G, Botezatu A. Epigenetic approaches for cervical neoplasia screening (Review). Exp Ther Med. 2021 Dec;22(6):1481. doi: 10.3892/etm.2021.10916. Epub 2021 Oct 25. PMID: 34765022; PMCID: PMC8576616. IF=2.75
