The role of heat shock factor 2 during Epstein-Barr virus infection
Kiiski, Jasmin (2023-05-09)
The role of heat shock factor 2 during Epstein-Barr virus infection
Kiiski, Jasmin
(09.05.2023)
Julkaisu on tekijänoikeussäännösten alainen. Teosta voi lukea ja tulostaa henkilökohtaista käyttöä varten. Käyttö kaupallisiin tarkoituksiin on kielletty.
suljettu
Julkaisun pysyvä osoite on:
https://urn.fi/URN:NBN:fi-fe2023060953728
https://urn.fi/URN:NBN:fi-fe2023060953728
Tiivistelmä
Epstein-Barr virus (EBV) infects over 90% of the world’s population. It establishes lifelong latent infections in its host. While most individuals are infected during childhood, and the infections remain mild or asymptomatic, in a small proportion of individuals EBV infection is associated with several malignant diseases including Burkitt lymphoma, Hodgkin lymphoma, gastric adenocarcinoma, and nasopharyngeal carcinoma. The association of EBV with multiple severe diseases and the fact that there are no approved antiviral drugs against EBV infection highlight the importance of developing drugs to combat the virus. Heat shock factors (HSFs) are a family of transcription factors that are crucial for all organisms to survive exposures to acute stress. Additionally, HSFs are activated by many other stimuli, mostly when cells undergo different environmental or internal conditions that challenge cellular homeostasis. Moreover, HSFs contribute to the pathogenesis of several cancers and neurodegenerative diseases. In humans, six members of the HSF family are identified. The focus of this thesis project is on HSF2, which is associated with cell differentiation and developmental processes, and it interacts with HSF1 during the heat shock response. Based on previous literature, viruses can use the host cell machinery to produce progeny virions. However, it is not known whether HSF2 contributes to any phase of EBV infection and viral replication. The aim of this study was to assess whether HSF2 plays a role in efficient EBV life cycle using knockout and overexpression cellular models. To study that, ectopically infected gastric adenocarcinoma (AGS) cell lines were used, and HSF2 knockout and HSF2 overexpression cell lines were generated. First, the levels of EBV-associated proteins were examined by western blotting. Then, using quantitative real-time PCR, the expression levels of EBV-associated genes, genes associated with DNA replication, and the amount of EBV genome copies were examined. The results obtained from this study provide new insights into the role of HSF2 in latent EBV infection. We showed that HSF2 plays a crucial role in viral DNA replication, and the absence of HSF2 decreases the expression of genes associated with DNA replication, thereby reducing the amount of EBV genome copies in EBV-infected cells. Accordingly, HSF2 overexpression leads to increased viral genome copies. Further research is needed to identify the mechanisms behind the reduction in EBV genome copies, but these results highlight the versatile functions and importance of HSF2 during latent EBV infection.