Meuris F, Carthagena L, Jaracz-Ros A, Gaudin F, Cutolo P, Deback C, et al. (2016) The CXCL12/CXCR4 Signaling Pathway: A New Susceptibility Factor in Human Papillomavirus Pathogenesis. PLoS Pathog 12(12): e1006039. https://doi.org/10.1371/journal.ppat.1006039
Abstract:
The productive human papillomavirus (HPV) life cycle is tightly linked to the differentiation and cycling of keratinocytes. Deregulation of these processes and stimulation of cell pro- liferation by the action of viral oncoproteins and host cell factors underlies HPV-mediated carcinogenesis. Severe HPV infections characterize the wart, hypogammaglobulinemia, infection, and myelokathexis (WHIM) immunodeficiency syndrome, which is caused by gain-of-function mutations in the CXCR4 receptor for the CXCL12 chemokine, one of which
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thelial organotypic cultures. Expression of CXCR41013 promoted stabilization of HPV onco- proteins, thus disturbing cell cycle progression and proliferation at the expense of the ordered expression of the viral genes required for virus production. Conversely, blocking CXCR41013 function restored virus production and limited HPV-induced carcinogenesis. Thus, CXCR4 and its potential activation by genetic alterations in the course of the carcino- genic process can be considered as an important host factor for HPV carcinogenesis.
License type:
http://creativecommons.org/licenses/by/4.0/
Funding Info:
This work was supported by the Institut National de la Sante´ et de la Recherche Me´dicale (FM, LC, CD, AJR, FG, PC, FB), ERA-Net for Research Programmes on Rare Diseases (WHIMThernet 2011-E-RARE 013-01) (FM, FB) and Institut National du Cancer (Chemokine-HPV TRANSLA11-077) (FM, CD, FB).