Vacinas terapêuticas contra proteínas E6 E E7 dos papilomavírus humanos (HPVs) de alto risco: um estudo de revisão
Carregando...
Data
2021-12-17
Autores
Rampazzo, Maria Luiza Zaniol
Título da Revista
ISSN da Revista
Título de Volume
Editor
Universidade Estadual Paulista (Unesp)
Resumo
O câncer cervical, ou câncer de colo de útero, é o terceiro tumor maligno mais frequente na população feminina e a terceira causa de morte de mulheres por câncer no mundo. A ligação entre as infecções genitais por HPV e o câncer cervical tem sido amplamente estudada. O HPV, infecção sexualmente transmissível, é a infecção viral mais comum do trato reprodutivo, e a maioria dos homens e mulheres sexualmente ativos serão infectados em algum momento de suas vidas. Existem cinco diferentes gêneros de papilomavírus encontrados em humanos - Alfa, Beta, Gama, Mu e Nu -, classificados de acordo com a análise da sequência de DNA, apresentam diferentes características de ciclo de vida e associações de doenças. O genoma viral é de DNA dupla fita, circular, com aproximadamente 8000 pares de bases, contendo oito diferentes genes denominados de fases de leitura aberta (ORFs) e uma região não codificadora longa de controle (LCR- Long Control Region). Essas regiões gênicas são responsáveis pela codificação de oito diferentes proteínas, que podem ser divididas em região precoce (E- early) e tardia (L- late), além da fase controladora LCR que contém a maioria dos elementos reguladores envolvidos na replicação e transcrição viral de DNA. A infecção inicial por HPV precisa de acesso às células da camada proliferativa basal do epitélio escamoso do colo uterino e ocorre através de micro abrasões. O modelo que tem sido postulado é de que o vírus inicialmente se anexa ao sulfato de heparano proteoglicano (HSPG) na membrana basal que pode atuar como receptor transitório para atrair o vírus para a superfície de queratinócitos. As proteínas iniciais E1 e E2, juntamente com os fatores de replicação do hospedeiro facilitam a replicação do DNA viral. Os genes E6 e E7 desempenham importante papel na carcinogênese induzida pelo HPV, interferindo nos genes supressores de tumor p53 e pRb, respectivamente, que são responsáveis por regular a proliferação celular normal. O HPV16 E5 tem demonstrado cooperar com E7 na transformação celular, ao inibir a resposta imunitária, com o aumento da motilidade celular e, também, tem demonstrado impedir a proliferação. A vacina profilática promove uma resposta humoral, a partir do contato com vírus-like particles (VLPs), ou partículas semelhantes ao vírus, que são caracterizadas pela morfologia semelhante ao vírus, porém destituídas de DNA viral, que é o responsável pelos danos da infecção por esse agente. As vacinas terapêuticas diferem das vacinas preventivas na medida em que se destinam a gerar imunidade mediada por células em vez de neutralizar anticorpos.
Cervical cancer is the third most common malignant tumor in the female population and the third leading cause of cancer death in women worldwide. The link between genital HPV infections and cervical cancer has been widely studied. HPV, a sexually transmitted infection, is the most common viral infection of the reproductive tract, and most sexually active men and women will be infected at some point in their lives. There are five different genera of papillomaviruses found in humans - Alpha, Beta, Gamma, Mu, and Nu - classified according to DNA sequence analysis, and showing different life cycle characteristics and disease associations. The viral genome is double-stranded circular DNA, with approximately 8000 base pairs, containing eight different genes called open reading frames (ORFs) and a non-coding long control region (LCR). These gene regions are responsible for encoding eight different proteins, which can be divided into early (E- early) and late (L- late) regions, in addition to the LCR-controlling phase that contains most of the regulatory elements involved in viral DNA replication and transcription. Initial HPV infection needs access to cells in the basal proliferative layer of the squamous epithelium of the cervix and occurs through micro abrasions. The model that has been postulated is that the virus initially attaches to heparan sulfate proteoglycan (HSPG) on the basal membrane which can act as a transient receptor to attract the virus to the surface of keratinocytes. The initial proteins E1 and E2, along with host replication factors facilitate viral DNA replication. The E6 and E7 genes play an important role in HPV-induced carcinogenesis by interfering with the tumor suppressor genes p53 and pRb, respectively, which are responsible for regulating normal cell proliferation. HPV16 E5 has been shown to cooperate with E7 in cell transformation by inhibiting the immune response, increasing cell motility, and has also been shown to inhibit proliferation. The prophylactic vaccine promotes a humoral response, from contact with virus-like particles (VLPs), or virus-like particles, which are characterized by virus-like morphology, but devoid of viral DNA, which is responsible for the damage of infection by this agent. Therapeutic vaccines differ from preventive vaccines in that they are intended to generate cell-mediated immunity rather than neutralize antibodies.
Cervical cancer is the third most common malignant tumor in the female population and the third leading cause of cancer death in women worldwide. The link between genital HPV infections and cervical cancer has been widely studied. HPV, a sexually transmitted infection, is the most common viral infection of the reproductive tract, and most sexually active men and women will be infected at some point in their lives. There are five different genera of papillomaviruses found in humans - Alpha, Beta, Gamma, Mu, and Nu - classified according to DNA sequence analysis, and showing different life cycle characteristics and disease associations. The viral genome is double-stranded circular DNA, with approximately 8000 base pairs, containing eight different genes called open reading frames (ORFs) and a non-coding long control region (LCR). These gene regions are responsible for encoding eight different proteins, which can be divided into early (E- early) and late (L- late) regions, in addition to the LCR-controlling phase that contains most of the regulatory elements involved in viral DNA replication and transcription. Initial HPV infection needs access to cells in the basal proliferative layer of the squamous epithelium of the cervix and occurs through micro abrasions. The model that has been postulated is that the virus initially attaches to heparan sulfate proteoglycan (HSPG) on the basal membrane which can act as a transient receptor to attract the virus to the surface of keratinocytes. The initial proteins E1 and E2, along with host replication factors facilitate viral DNA replication. The E6 and E7 genes play an important role in HPV-induced carcinogenesis by interfering with the tumor suppressor genes p53 and pRb, respectively, which are responsible for regulating normal cell proliferation. HPV16 E5 has been shown to cooperate with E7 in cell transformation by inhibiting the immune response, increasing cell motility, and has also been shown to inhibit proliferation. The prophylactic vaccine promotes a humoral response, from contact with virus-like particles (VLPs), or virus-like particles, which are characterized by virus-like morphology, but devoid of viral DNA, which is responsible for the damage of infection by this agent. Therapeutic vaccines differ from preventive vaccines in that they are intended to generate cell-mediated immunity rather than neutralize antibodies.
Descrição
Palavras-chave
câncer cervical, vacina profilática, vacina terapêutica, HPV, proteínas oncogênicas, cervical cancer, prophylactic vaccine, therapeutic vaccine, oncogenic proteins