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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

E6/E7 Functional Differences among Two Natural Human Papillomavirus 18 Variants in Human Keratinocytes

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Author(s):
Nunes, Emily Montosa [1] ; Talpe-Nunes, Valeria [1] ; Sobrinho, Joao Simao [1] ; Ferreira, Silvaneide [1] ; Lino, Vanesca de Souza [2] ; Termini, Lara [1] ; Fernandes Silva, Gabriela Avila [1] ; Boccardo, Enrique [2] ; Villa, Luisa Lina [1, 3] ; Sichero, Laura [1]
Total Authors: 10
Affiliation:
[1] Univ Sao Paulo HCFMUSP, Ctr Translat Res Oncol, Inst Canc Estado Sao Paulo ICESP, Hosp Clin, Fac Med, BR-01246000 Sao Paulo - Brazil
[2] Univ Sao Paulo, Inst Ciencias Biomed, Dept Microbiol, BR-05508900 Sao Paulo - Brazil
[3] Univ Sao Paulo, Fac Med, Dept Radiol & Oncol, BR-01246000 Sao Paulo - Brazil
Total Affiliations: 3
Document type: Journal article
Source: Viruses-Basel; v. 13, n. 6 JUN 2021.
Web of Science Citations: 0
Abstract

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. (AU)

FAPESP's process: 15/26346-6 - Biological and biochemical properties of natural variants of HPV-18
Grantee:Emily Montosa Nunes
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 15/26345-0 - Impact of of E6/E7 genetic variability upon the oncogenic potential of HPV-18
Grantee:Laura Cristina Sichero Vettorazzo
Support type: Regular Research Grants
FAPESP's process: 17/02997-3 - Role of the protein RECK in HPV-mediated cell transformation
Grantee:Enrique Mario Boccardo Pierulivo
Support type: Regular Research Grants