Tetraspanin CD9 affects HPV16 infection by modulating ADAM17 activity and the ERK signalling pathway.
ADAM17 Protein
/ genetics
Endocytosis
Gene Expression Regulation
Gene Knockdown Techniques
HaCaT Cells
HeLa Cells
Human papillomavirus 16
Humans
Keratinocytes
/ virology
MAP Kinase Signaling System
Papillomavirus Infections
/ metabolism
Tetraspanin 29
/ genetics
Transforming Growth Factor alpha
/ metabolism
Virus Internalization
ADAM17
CD9
Entry
HPV
Infection
L1
Papillomavirus
Receptor
TSPAN29
Tetraspanin
Journal
Medical microbiology and immunology
ISSN: 1432-1831
Titre abrégé: Med Microbiol Immunol
Pays: Germany
ID NLM: 0314524
Informations de publication
Date de publication:
Aug 2020
Aug 2020
Historique:
received:
29
01
2020
accepted:
24
03
2020
pubmed:
10
5
2020
medline:
26
1
2021
entrez:
10
5
2020
Statut:
ppublish
Résumé
Human papillomaviruses (HPV) are causative agents of various tumours such as cervical cancer. HPV binding to the cell surface of keratinocytes leads to virus endocytosis at tetraspanin enriched microdomains. Complex interactions of the capsid proteins with host proteins as well as ADAM17-dependent ERK1/2 signal transduction enable the entry platform assembly of the oncogenic HPV type 16. Here, we studied the importance of tetraspanin CD9, also known as TSPAN29, in HPV16 infection of different epithelial cells. We found that both overexpression and loss of the tetraspanin decreased infection rates in cells with low endogenous CD9 levels, while reduction of CD9 expression in keratinocytes that exhibit high-CD9 protein amounts, led to an increase of infection. Therefore, we concluded that low-CD9 supports infection. Moreover, we found that changes in CD9 amounts affect the shedding of the ADAM17 substrate transforming growth factor alpha (TGFα) and the downstream phosphorylation of ERK. These effects correlate with those on infection rates suggesting that a specific CD9 optimum promotes ADAM17 activity, ERK signalling and virus infection. Together, our findings implicate that CD9 regulates HPV16 infection through the modulation of ADAM17 sheddase activity.
Identifiants
pubmed: 32385608
doi: 10.1007/s00430-020-00671-5
pii: 10.1007/s00430-020-00671-5
pmc: PMC7206579
doi:
Substances chimiques
CD9 protein, human
0
TGFA protein, human
0
Tetraspanin 29
0
Transforming Growth Factor alpha
0
ADAM17 Protein
EC 3.4.24.86
ADAM17 protein, human
EC 3.4.24.86
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
461-471Subventions
Organisme : Deutsche Forschungsgemeinschaft
ID : FL 696/3-1
Organisme : Deutsche Forschungsgemeinschaft
ID : 125440785 -SFB877 (A4)
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