Caracterização molecular dos HPVs de alto risco dos genótipos -53, -56 e -66 infectando mulheres no Distrito Federal e entorno

AUTOR(ES)

Patrícia Soares Wyant

DATA DE PUBLICAÇÃO

2007

RESUMO

Cervical cancer is the second major cause of death in the female population and is associated with human papillomavirus (HPV) infection. Different HPV genotypes have different oncogenic potential, and different variants intragenotype can also present different oncogenic potential. Several works have been done with the aim of describing HPV-16 and -18 variants. However, there is little information about variants of the other high-risk genotypes. The aim of this study was to improve the knowledge about genetic variability of HPVs-53, -56, and -66. We amplified and sequenced the LCR, E6 and L1 genomic regions of six HPV-53, five HPV-56 and six HPV-66 isolates. The sequences were compared to the reference sequences of HPVs-53, -56 and -66 to evaluate the presence of nucleotide substitutions. We also performed a phylogenetic analysis with the Federal District (DF) isolates and those of other parts of the world, using sequences from the GenBank. The analysis of the HPV-53 E6 and LCR isolates showed the presence of six variants in comparison with the reference sequence. In the analysis of the L1 gene we detected 3 variants. The analysis of HPV-56 E6 and LCR isolates showed the presence of 3 variants. On the L1 gene, 1 variant was detected. The analysis of HPV-66 isolates revealed the presence of one variant in E6 and 2 variants in L1, no variants were found in LCR. There were observed non-synonymous nucleotide substitutions, leading to amino acid exchanges, which may indicate a biological and pathogenic diversity between the HPVs genotypes. Furthermore, the substitutions detected on the putative transcription factors binding sites may have some implication on viral oncogenes expression. The phylogenetic analysis of HPVs-53 and -56 did not show ethno-geographical clustering that could be correlated with the detected variants, as observed for HPV-16 and -18. The HPVs-53, -56 and -66 phylogenetic analysis showed a dichotomic division only described to subtypes analysis. Phylogenetically, the HPV-66 was the most conserved genotype, with isolates from many regions clustering in the same branch, with the reference sequence. More studies must be conducted to clarify the impact of the variations found in this study, once they can interfere with the viral infectivity and pathogenicity.

ASSUNTO(S)

câncer biologia molecular mulheres - doenças - distrito federal (brasil) vírus do papiloma

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