Human papillomavirus type 16 E6 induces cell competition.
Journal
PLoS pathogens
ISSN: 1553-7374
Titre abrégé: PLoS Pathog
Pays: United States
ID NLM: 101238921
Informations de publication
Date de publication:
03 2022
03 2022
Historique:
received:
08
01
2022
accepted:
10
03
2022
revised:
04
04
2022
pubmed:
24
3
2022
medline:
7
4
2022
entrez:
23
3
2022
Statut:
epublish
Résumé
High-risk human papillomavirus (HPV) infections induce squamous epithelial tumors in which the virus replicates. Initially, the virus-infected cells are untransformed, but expand in both number and area at the expense of uninfected squamous epithelial cells. We have developed an in vitro assay in which colonies of post-confluent HPV16 expressing cells outcompete and displace confluent surrounding uninfected keratinocytes. The enhanced colony competition induced by the complete HPV16 genome is conferred by E6 expression alone, not by individual expression of E5 or E7, and requires E6 interaction with p53. E6-expressing keratinocytes undermine and displace adjacent normal keratinocytes from contact with the attachment substrate, thereby expanding the area of the E6-expressing colony at the expense of normal keratinocytes. These new results separate classic oncogenicity that is primarily conferred by HPV16 E7 from cell competition that we show is primarily conferred by E6 and provides a new biological role for E6 oncoproteins from high-risk human papillomaviruses.
Identifiants
pubmed: 35320322
doi: 10.1371/journal.ppat.1010431
pii: PPATHOGENS-D-21-02632
pmc: PMC8979454
doi:
Substances chimiques
Oncogene Proteins, Viral
0
Papillomavirus E7 Proteins
0
Repressor Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1010431Subventions
Organisme : NIAID NIH HHS
ID : R01 AI158426
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA134737
Pays : United States
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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