E6/E7 Functional Differences among Two Natural Human Papillomavirus 18 Variants in Human Keratinocytes
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Citações na Scopus
2
Tipo de produção
article
Data de publicação
2021
Título da Revista
ISSN da Revista
Título do Volume
Editora
MDPI
Autores
LINO, Vanesca de Souza
BOCCARDO, Enrique
Citação
VIRUSES-BASEL, v.13, n.6, article ID 1114, 17p, 2021
Resumo
It is suggested that HPV-18 variants from the A lineage have higher oncogenic potential compared to B variants. Some studies show uneven distribution of HPV-18 variants in cervical adenocarcinomas and squamous cell carcinomas. Regarding HPV-18 variants' functions, the few studies reported focus on E6, and none were performed using natural host cells. Here, we immortalized primary human keratinocytes (PHKs) with E6/E7 of HPV-18 A1 and B1 sublineages and functionally characterized these cells. PHK18A1 reached immortalization significantly faster than PHK18B1 and formed a higher number of colonies in monolayer and 3D cultures. Moreover, PHK18A1 showed greater invasion ability and higher resistance to apoptosis induced by actinomycin-D. Nevertheless, no differences were observed regarding morphology, proliferation after immortalization, migration, or epithelial development in raft cultures. Noteworthy, our study highlights qualitative differences among HPV-18 A1 and B1 immortalized PHKs: in contrast to PHK18A1, which formed more compact colonies and spheroids of firmly grouped cells and tended to invade and migrate as clustered cells, morphologically, PHK18B1 colonies and spheroids were looser, and migration and invasion of single cells were observed. Although these observations may be relevant for the association of these variants with cervical cancer of different histological subtypes, further studies are warranted to elucidate the mechanisms behind these findings.
Palavras-chave
HPV-18, oncogenic potential, molecular variant, cell transformation, immortalization
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