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Methylation of the regulatory sequences of integrated and extrachromosomal form of HPV 16 in tonsillar tumors
Pokrývková, Barbora ; Tachezy, Ruth (advisor) ; Hubáček, Petr (referee)
Human papillomavirus is connected with induction of cervical carcinoma as well as for some other anogenital carcinomas and subset of carcinomas of head and neck. Presence of viral E6 and E7 oncoproteins may induce cell transformation, higher load of oncoproteins is caused by the regulatory E2 protein inactivation. Aims of recent study are mechanisms of E2 protein inactivation. One option is integration of viral DNA into the host genome, which is located into the E2 gene region. Some carcinomas, where virus with extrachromosomal form was presented, were found. It appears that epigenetic changes can play the role in the development of this type of tumors, especially DNA methylation or mutation in the regulatory region of the virus. The methylation degree analysis on samples of tonsillar carcinomas with extrachromosomal and integrated form of the virus was conduced, as well as viral load of both groups was compared and the expression of E6 and E7 gene was confirmed. The results of methylation analysis showed increased methylation of the virus with integrated DNA. Mutations in the E2 protein binding sites are not revealed. The expression of the viral oncogenes were confirmed in all tumors regardless of the form of the viral genome. The mechanism of tumors induction, especially for virus with...
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Intracellular restriction factors of small DNA viruses
Anderová, Karolína ; Forstová, Jitka (advisor) ; Pokrývková, Barbora (referee)
The theme of this work is to summarize knowledge about protein restriction factors, which function in cells infected by small DNA viruses of families Hepadnaviridae, Parvoviridae, Polyomaviridae and Papillomaviridae. Both restriction factors induced by interferon and restriction factors of intrinsic immunity which are constitutively produced in cells are included in this work. At the same time, mechanisms by which viruses overcome the inhibition effects of restriction factors are mentioned. Restriction factors suppressing Hepatitis B virus infection like components of PML nuclear bodies and proteins Smc5/6, SAMHD1, APOBEC, TRIM, ZAP and Tetherin are described. For the representatives of Parvoviridae family, deaminases APOBEC and PML protein were identified as restriction factors. For the infection by polyomaviruses, restriction factors FAM111A and SRSF1 were described. Restriction by PML nuclear bodies and its component Sp100 and proteins APOBEC, IFI16 and IFIT1 is discussed for the Papillomaviridae family. Keywords: small DNA viruses, intracellular DNA sensing, restriction factors, viral antagonistic mechanisms
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Methylation of the regulatory sequences of integrated and extrachromosomal form of HPV 16 in tonsillar tumors
Pokrývková, Barbora ; Tachezy, Ruth (advisor) ; Hubáček, Petr (referee)
Human papillomavirus is connected with induction of cervical carcinoma as well as for some other anogenital carcinomas and subset of carcinomas of head and neck. Presence of viral E6 and E7 oncoproteins may induce cell transformation, higher load of oncoproteins is caused by the regulatory E2 protein inactivation. Aims of recent study are mechanisms of E2 protein inactivation. One option is integration of viral DNA into the host genome, which is located into the E2 gene region. Some carcinomas, where virus with extrachromosomal form was presented, were found. It appears that epigenetic changes can play the role in the development of this type of tumors, especially DNA methylation or mutation in the regulatory region of the virus. The methylation degree analysis on samples of tonsillar carcinomas with extrachromosomal and integrated form of the virus was conduced, as well as viral load of both groups was compared and the expression of E6 and E7 gene was confirmed. The results of methylation analysis showed increased methylation of the virus with integrated DNA. Mutations in the E2 protein binding sites are not revealed. The expression of the viral oncogenes were confirmed in all tumors regardless of the form of the viral genome. The mechanism of tumors induction, especially for virus with...
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Molecular mechanisms of carcinogenesis induced by HPV from Alpha and Betapapillomaviridae
Pokrývková, Barbora ; Tachezy, Ruth (advisor) ; Dvořáček, Lukáš (referee)
Human papillomaviruses (HPV) are small DNA viruses ubiquitously present in population. They infect mucosal and cutaneous epithelium and cause benign and malignant diseases. Research of HPV became more intensive after 1983, when these viruses were isolated for the first time from cervical carcinoma samples. Nowaday it is known, that number of other malignancies is associated with HR HPV infection and the research is focused on evaluating the role of these viruses in skin cancer. This bachelor thesis outlines mechanisms by which HPV from Alfa and Betapapillomaviridae genus causes malignant and benign lesions. The main HPV oncoprotein is protein E6, which binds p53 and targets it for degradation, and protein E7 which interacts with retinoblastoma protein and influences his function in cell cycle regulation. Papillomaviruses from genus alpha contain additionally E5 oncoprotein which is not present in viruses from genus beta. This suggests that the mechanisms of cancerogenesis initiated by viruses from these two genera will be different. Powered by TCPDF (www.tcpdf.org)
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