Molecular Bases of Human Papillomavirus Pathogenesis in the Development of Cervical Cancer

Pedroza-Saavedra, Adolfo; Plett-Torres, Tanya; Chihu-Amparán, Lilia; Maldonado-Gama, Minerva; Gonzalez-Jaimes, A.; Esquivel-Guadarrama, Fernando; Gutiérrez‐Xicoténcatl, Lourdes

doi:10.5772/29020

Cited by 4 publications

(5 citation statements)

References 272 publications

(210 reference statements)

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“…Em HPV16 a oncoproteína E5 é uma proteína transmembrana do tipo α-hélice, de caráter hidrofóbica e constituída por um total de 83 aminoácidos. De acordo com Saavedra et al (2012), na estrutura secundária do oncogene E5 do HPV16, representada pela sequência de referência K02718, são distinguíveis três regiões importantes para o funcionamento desta oncoproteína: (1) região localizada entre os aminoácidos 1 e 30, responsável pela localização celular e ancoragem independente de crescimento, (2) região localizada entre os aminoácidos 41 e 54 e (3) região localizada entre os aminoácidos 54 ao 78, ambas contendo domínios de ligação da subunidade da bomba de prótons ATPase-16 kDa, responsável pela acidificação dos endossomos.…”

Section: Resultsunclassified

“…Estruturalmente, 16E5 corresponde a uma proteína α-hélice transmembrana (BIBLE et al, 2000;NATH et al, 2006;SAAVEDRA et al, 2012). Plesa et al (2014) realizaram uma análise dos polimorfismos circulantes na Romênia e as mutações mais prevalentes foram T3904A, T3910C, G3919C, T3928C, A3978C, T3988C, T3991G, T4033C, A4041G/C, onde os respectivos códons mutantes passaram a ser representados pelos seguintes resíduos de aminoácidos: F19I, V21A, C24S, L27P, I44L, L47S, L48A, V62A, I65V/L.…”

Section: Resultsunclassified

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Análise in Silico Da Variabilidade Genética Do Oncogene E5 Do HPV 16

Matos¹,

Matos²

2023

TeS

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RESUMO -Introdução: O Papilomavírus humano (HPV) é o responsável por causar diversos tipos de cânceres, destacando-se o cervical, e as lesões genitais, sendo o oncogene E5 pertencente a esse patógeno importante para seu potencial oncogênico. Objetivo: Analisar a variabilidade genética in silico do gene E5 das sequências gênicas do HPV 16. Método: Trata-se de um estudo descritivo, quanti-qualitativo, ao apresentar o mapeamento e quantificar as regiões polimórficas do gene E5. Para a coleta das sequencias gênicas, foi utilizado o banco de dados genômicos do National Center for Biotechnology Information (NCBI). As sequências gênicas foram coletadas no formato FASTA. Posteriormente, foi utilizado o programa CLUSTALW, do pacote de dados do software MEGA6, para a realização do alinhamento múltiplo das sequências, permitindo a identificação de sítios polimórficos entre duas ou mais sequências gênicas. Resultados: As análises das variações do oncogene E5 do HPV16 revelaram a existência de vários sítios polimórficos, bem como as variações encontradas nas sequencias das variantes, em relação à sequência protótipo K02718. Em relação ao mapeamento dos epítopos foi observado que a sequência da oncoproteína 16E5 da amostra de referência K02718, formou epítopos imunogênicos com moléculas pertencentes ao MHC-I (HLA-A e HLA-B) e MHC-II (HLADR), sendo as moléculas

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Section: Resultsunclassified

Análise in Silico Da Variabilidade Genética Do Oncogene E5 Do HPV 16

Matos¹,

Matos²

2023

TeS

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“…The NF-κB pathway corresponds to a family of transcriptional factors that bind to responsive κB sequences found in DNA. These factors are responsible for expressing genes related to the inflammatory response, proliferation, differentiation, adhesion, and apoptosis [66][67][68][69][70][71]. The exaggerated or even constitutive activation of the pathway has been detected in many human diseases [72].…”

Section: Discussionmentioning

confidence: 99%

Identification and Functional Implications of the E5 Oncogene Polymorphisms of Human Papillomavirus Type 16

da Silva-Júnior,

de Oliveira Silva,

Gurgel

et al. 2024

TropicalMed

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The persistence of the human papillomavirus type 16 (HPV16) infection on the cervical epithelium contributes to the progression of cervical cancer. Studies have demonstrated that HPV16 genetic variants may be associated with different risks of developing cervical cancer. However, the E5 oncoprotein of HPV16, which is related to several cellular mechanisms in the initial phases of the infection and thus contributes to carcinogenesis, is still little studied. Here we investigate the HPV16 E5 oncogene variants to assess the effects of different mutations on the biological function of the E5 protein. We detected and analyzed the HPV16 E5 oncogene polymorphisms and their phylogenetic relationships. After that, we proposed a tertiary structure analysis of the protein variants, preferential codon usage, and functional activity of the HPV16 E5 protein. Intra-type variants were grouped in the lineages A and D using in silico analysis. The mutations in E5 were located in the T-cell epitopes region. We therefore analyzed the interference of the HPV16 E5 protein in the NF-kB pathway. Our results showed that the variants HPV16E5_49PE and HPV16E5_85PE did not increase the potential of the pathway activation capacity. This study provides additional knowledge about the mechanisms of dispersion of the HPV16 E5 variants, providing evidence that these variants may be relevant to the modulation of the NF-κB signaling pathway.

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“…Parfenov and colleagues found a higher expression of E2, E4, and E5 than of E6/E7 when HPV is not integrated into the cellular genome [99,100]. Once the viral genome integrated, a high expression of E6/E7 and loss of E2, E4, and E5 expression was observed, allowing the carcinogenic process to initiate (Table 3) [12]. Cellular gene alterations were also significantly studied in HPV-positive and negative HNSCC and performed with samples from women and men.…”

Section: Head and Neck Squamous Cell Carcinomamentioning

confidence: 99%

“…During the viral genome insertion, the expression of E5 is also lost, which initially functions in maintaining cell proliferation through the EGFR. Altogether, these events ultimately lead to a transformed phenotype [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

The Immune Response Generated against HPV Infection in Men and Its Implications in the Diagnosis of Cancer

Chihu-Amparan

Pedroza-Saavedra

Gutiérrez‐Xicoténcatl

2023

Microorganisms

Self Cite

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Human papillomavirus (HPV) infection is associated with precancerous lesions and cancer of the genital tract both in women and men. The high incidence of cervical cancer worldwide focused the research on this infection mainly in women and to a lesser extent in men. In this review, we summarized epidemiological, immunological, and diagnostic data associated with HPV and cancer in men. We presented an overview of the main characteristics of HPV and infection in men that are associated with different types of cancer but also associated with male infertility. Men are considered important vectors of HPV transmission to women; therefore, identifying the sexual and social behavioral risk factors associated with HPV infection in men is critical to understand the etiology of the disease. It is also essential to describe how the immune response develops in men during HPV infection or when vaccinated, since this knowledge could help to control the viral transmission to women, decreasing the incidence of cervical cancer, but also could reduce other HPV-associated cancers among men who have sex with men (MSM). Finally, we summarized the methods used over time to detect and genotype HPV genomes, as well as some diagnostic tests that use cellular and viral biomarkers that were identified in HPV-related cancers.

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Molecular Bases of Human Papillomavirus Pathogenesis in the Development of Cervical Cancer

Cited by 4 publications

References 272 publications

Análise in Silico Da Variabilidade Genética Do Oncogene E5 Do HPV 16

Análise in Silico Da Variabilidade Genética Do Oncogene E5 Do HPV 16

Identification and Functional Implications of the E5 Oncogene Polymorphisms of Human Papillomavirus Type 16

The Immune Response Generated against HPV Infection in Men and Its Implications in the Diagnosis of Cancer

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