Dataset Information

Analysis of Nucleotide Alterations in the E6 Genomic Region of Human Papillomavirus Types 6 and 11 in Condyloma Acuminatum Samples from Brazil.

ABSTRACT: Condyloma acuminata (CA), or genital warts, are benign proliferative epidermal or mucous lesions that are caused by infection with human papillomavirus (HPV), mainly the low-risk types 6 and 11. HPV variants are defined as viral sequences that share identity in the nucleotide sequence of the L1 gene greater than 98%. Based on this criterion, HPV6 and 11 variant lineages have been studied, and there are ongoing attempts to correlate these genetic variants with different clinical findings of infection. Therefore, the aims of this study were to detect variants and nucleotide alterations present in the E6 regions of HPV types 6 and 11 found in CA samples, to correlate the HPV presence with the clinical-pathological data of the patients, and to determine phylogenetic relationships with variants from other places in the world. The E6 regions of 25 HPV6 samples and 7 HPV11 samples from CA were amplified using PCR with specific primers. The products were ligated to a cloning vector and five colonies of each sample were sequenced to observe the nucleotide alterations. Twelve samples were identified as the HPV6B3 variant, presenting the mutation (guanine) G474A (adenine), and one of them also showed the mutation (thymine) T369G. The other 13 patients were positive for HPV6B1 without nucleotide alterations. In the analysis of the HPV11 samples, all patients showed the mutations T137C and (cytosine) C380T. One patient also presented the nucleotide alteration T410C. None of the mutations found in the 32 analyzed samples resulted in amino acid changes. Patient age, local occurrence, and HIV infection did not show significant association with HPV infection. Besides, the data found in this study did not show a relationship with the geographical region of isolation when compared to other data from different regions of the world. In this way, despite the nucleotide alterations found, it was not possible to observe amino acid changes and variants grouping according to geographical region.

SUBMITTER: Dias MC

PROVIDER: S-EPMC6521423 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Analysis of Nucleotide Alterations in the E6 Genomic Region of Human Papillomavirus Types 6 and 11 in Condyloma Acuminatum Samples from Brazil.

Dias Marina Carrara MC Stuqui Bruna B Provazzi Paola Jocelan Scarin PJS Bittar Cíntia C Candido Natália Maria NM de Matos Renata Prandini Adum RPA Badial Rodolfo Miglioli RM do Bonfim Caroline Measso CM Melli Patricia Pereira Dos Santos PPDS Quintana Silvana Maria SM Cordeiro José Antônio JA Rahal Paula P Calmon Marilia de Freitas MF

Advances in virology 20190502

Condyloma acuminata (CA), or genital warts, are benign proliferative epidermal or mucous lesions that are caused by infection with human papillomavirus (HPV), mainly the low-risk types 6 and 11. HPV variants are defined as viral sequences that share identity in the nucleotide sequence of the L1 gene greater than 98%. Based on this criterion, HPV6 and 11 variant lineages have been studied, and there are ongoing attempts to correlate these genetic variants with different clinical findings of infec ...[more]

PMID: 31186642

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Project description:BackgroundCondyloma acuminatum (CA) is a sexually transmitted disease characterized by the anomalous proliferation of keratinocytes caused by human papillomavirus (HPV) infection. Fu Fang Gang Liu liquid (FFGL) is an effective externally administered prescription used to treat CA; however, its molecular mechanism remains unclear. This study aimed to identify and experimentally validate the major active ingredients and prospective targets of FFGL.MethodsNetwork pharmacology, transcriptomics, and enrichment analysis were used to identify the active ingredients and prospective targets of FFGL, which were confirmed through subsequent experimental validation using mass spectrometry, molecular docking, western blotting, and in vitro assays.ResultsThe network pharmacology analysis revealed that FFGL contains a total of 78 active compounds, which led to the screening of 610 compound-related targets. Among them, 59 overlapped with CA targets and were considered to be targets with potential therapeutic effects. The protein-protein interaction network analysis revealed that protein kinase B (Akt) serine/threonine kinase 1 was a potential therapeutic target. To further confirm this result, we performed ribonucleic acid sequencing (RNA-seq) assays on HPV 18+ cells after FFGL exposure and conducted enrichment analyses on the differentially expressed genes that were screened. The enrichment analysis results indicated that the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathway may be a key pathway through which FFGL exerts its effects. Further in vitro experiments revealed that FFGL significantly inhibited the activity of HPV 18+ cells and reduced PI3K and Akt protein levels. A rescue experiment indicated that the reduction in cell viability induced by FFGL was partially restored after the administration of activators of the PI3K/Akt pathway. We further screened two active components of FFCL that may be efficacious in the treatment of CA: periplogenin and periplocymarin. The molecular docking experiments showed that these two compounds exhibited good binding activity to Akt1.ConclusionFFGL reduced HPV 18+ cell viability by inhibiting key proteins in the PI3K/Akt pathway; this pathway may represent an essential mechanism through which FFGL treats CA. Periplogenin and periplocymarin may play a significant role in this process.

Dataset Information

Analysis of Nucleotide Alterations in the E6 Genomic Region of Human Papillomavirus Types 6 and 11 in Condyloma Acuminatum Samples from Brazil.

Publications

Analysis of Nucleotide Alterations in the E6 Genomic Region of Human Papillomavirus Types 6 and 11 in Condyloma Acuminatum Samples from Brazil.

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