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001-es BibID:BIBFORM065244
Első szerző:Ferenczi Annamária (molekuláris biológus, mikrobiológus)
Cím:Phylogenetic and functional analysis of sequence variation of human papillomavirus type 31 E6 and E7 oncoproteins / Annamária Ferenczi, Eszter Gyöngyösi, Anita Szalmás, Brigitta László, József Kónya, György Veress
Dátum:2016
ISSN:1567-1348
Megjegyzések:High-risk human papillomaviruses (HPV) are the causative agents of cervical and other anogenital cancers as well as a subset of head and neck cancers. The E6 and E7 oncoproteins of HPV contribute to oncogenesis by associating with the tumour suppressor protein p53 and pRb, respectively. For HPV types 16 and 18, intratypic sequence variation was shown to have biological and clinical significance. The functional significance of sequence variation among HPV 31 variants was studied less intensively. HPV 31 variants belonging to different variant lineages were found to have differences in persistence and in the ability to cause high grade cervical intraepithelial neoplasia. In the present study, we started to explore the functional effects of natural sequence variation of HPV 31 E6 and E7 oncoproteins. The E6 variants were tested for their effects on p53 protein stability and transcriptional activity, while the E7 variants were tested for their effects on pRb protein level and also on the transcriptional activity of E2F transcription factors. HPV 31 E7 variants displayed uniform effects on pRb stability and also on the activity of E2F transcription factors. HPV 31 E6 variants had remarkable differences in the ability to inhibit the trans-activation function of p53 but not in the ability to induce the in vivo degradation of p53. Our results indicate that natural sequence variation of the HPV 31 E6 protein may be involved in the observed differences in the oncogenic potential between HPV 31 variants.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
human papillomavirus
type 31
E6
E7
variants
functional analysis
Megjelenés:Infection, Genetics and Evolution 43 (2016), p. 94-100. -
További szerzők:Gyöngyösi Eszter (1983-) (molekuláris biológus, mikrobiológus) Szalmás Anita (1978-) (biológus, mikrobiológus, klinikai mikrobiológus) László Brigitta (1983-) (molekuláris biológus, mikrobiológus) Kónya József (1964-) (szakorvos, klinikai mikrobiológus) Veress György (1966-) (biológus, mikrobiológus)
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2.

001-es BibID:BIBFORM096437
Első szerző:Nagy Zsófia (molekuláris biológus)
Cím:Effect of E2 and long control region polymorphisms on disease severity in human papillomavirus type 11 mediated mucosal disease : protein modelling and functional analysis / Zsófia Nagy, Zoltán Pethő, Gábor Kardos, Tamás Major, Attila Szűcs, Krisztina Szarka
Dátum:2021
ISSN:1567-1348
Megjegyzések:Interaction of the long control region (LCR) and the E2 protein of HPV11s was studied by in silico modelling and in vitro functional analysis. Genomes of HPV11s from fifteen (six known and nine novel) patients (two solitary papillomas, eleven respiratory papillomatoses of different severity, one condyloma acuminatum and one cervical atypia) were sequenced; E2 polymorphisms were analysed in silico by protein modelling. E2 and LCR variants were cloned into pcDNA3.1+ expression vector and into pALuc reporter vector, respectively, transfected to HEp2 cells alone or in different combinations and the luciferase activity was measured. In the E2, the ubiquitous polymorphism K308R caused stronger binding between the dimers but did not alter DNA binding; E2s with this polymorphism were significantly less efficient than the reference in promoting LCR activity. The unique polymorphism Q86K changed the negative surface charge of E2 (Q86) to positive (K86). The unique polymorphisms S245F and N247T in the hinge region disrupt a probable phosphorylation site in a RXXS motif targeted by protein kinase A and B, but do not affect directly the amino acids critical to nuclear transport. Both unique patterns partly restored the LCR activating potential disrupted by K308R. A unique E2/E4 ORF with a 58-bp deletion leading to a frameshift and an early stop codon resulted in a practically nonfunctional E2, and was associated with a papillomatosis with dysplasia. When testing existing LCR-E2 combinations, LCR with intrinsically lower enhancer capacity was only marginally activated by its E2 (R308 and the deletion mutant), and did not significantly exceed the activity of the reference LCR without E2. Combined with more potent LCRs associated with more severe disease, the activity was significantly higher, but still significantly lower than LCRs with reference E2. In summary, LCR-E2 interaction determined by their polymorphisms may explain, at least partly, differences in disease severity.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Low-risk human papillomavirus
Recurrent respiratory papillomatosis
Genome polymorphisms
Long control region
Transactivating potential
Megjelenés:Infection Genetics and Evolution. - 93 (2021), p. 1-13. -
További szerzők:Pethő Zoltán (1989-) (orvos) Kardos Gábor (1974-) (szakorvos, klinikai mikrobiológus) Major Tamás (1973-) (fül-orr-gégész) Szűcs Attila (1970-) (fül-orr-gégész) Szarka Krisztina (1971-) (molekuláris biológus, mikrobiológus)
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Intézményi repozitóriumban (DEA) tárolt változat
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3.

001-es BibID:BIBFORM082111
Első szerző:Szinai Mihály
Cím:Comparative analysis of human papillomavirus type 6 complete genomes originated from head and neck and anogenital disorders / Szinai Mihály, Nagy Zsófia, Máté Petra, Kovács Dávid, Laczkó Levente, Kardos Gábor, Sápy Tamás, Szűcs Attila, Szarka Krisztina
Dátum:2019
ISSN:1567-1348
Megjegyzések:It is increasingly recognized that fundamental differences exist between high-risk and low-risk human papillomavirus (HPV) genotypes regarding interactions with the host. This study aims to join the recently emerging efforts to uncover these differences at the complete genome level and to study how they may influence the disease caused. Sixteen samples of thirteen patients with various HPV6-mediated benign mucosal disorders (nine recurrent respiratory papillomatoses with 2-8 recurrences, one condyloma acuminatum and three premalignant lesions of the genital mucosa) were sampled to determine the complete virus genomes. We collected the 197 HPV6 complete genomes deposited in the GenBank for cluster analysis to determine (sub)lineages. Genome polymorphisms were determined against the reference sequences of the (sub)lineages. Genome polymorphisms of the long control region (LCR) were tested for putative transcription factor binding sites; their functional analysis was performed by transient transfection of cloned whole LCRs into HEp-2 cells using a luciferase reporter system. Genomes from the same patients were always identical. Three, nine and one patients carried HPV6 lineage A, sublineage B1 and B2 variants, respectively. The three lineage A sequences were highly similar to each other, but distinct from the reference genome. A unique non-synonymous single nucleotide polymorphism (SNP) was found in the E5a open reading frame (ORF). Sublineage B1 genomes were more diverse, exhibited unique non-synonymous SNPs in the LCR and the E2/E4, L1, L2 ORFs. LCR activity of lineage A and sublineage B1 differed significantly; activity of one sublineage B1 LCR exhibiting two unique SNPs was significantly higher than that of other B1 LCR variants, close to the mean of LCR activities of lineage A variants. Different HPV6 lineages showed marked differences in variability patterns of the different genome regions. This may be involved in the differences in their distribution in different diseases or patient populations.
Tárgyszavak:Orvostudományok Egészségtudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Cervical atypia
Condyloma acuminatum
Genome polymorphisms
Intratypic variation
Low-risk human papillomavirus
Recurrent respiratory papillomatosis
Megjelenés:INFECTION GENETICS AND EVOLUTION. - 71 (2019), p. 140-150. -
További szerzők:Nagy Zsófia (1991-) (molekuláris biológus) Máté Petra Kovács Dávid (1989-) (fül-orr-gégész) Laczkó Levente (1992-) (biológus) Kardos Gábor (1974-) (szakorvos, klinikai mikrobiológus) Sápy Tamás (1970-) (szülész-nőgyógyász) Szűcs Attila (1970-) (fül-orr-gégész) Szarka Krisztina (1971-) (molekuláris biológus, mikrobiológus)
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