Abstract:
:Several lines of evidence indicate that cutaneous human papillomavirus (HPV) types belonging to the beta genus of the HPV phylogenetic tree synergize with UV radiation in the development of skin cancer. Accordingly, the E6 and E7 oncoproteins from some beta HPV types are able to deregulate pathways related to immune response and cellular transformation. Toll-like receptor 9 (TLR9), in addition to playing a role in innate immunity, has been shown to be involved in the cellular stress response. Using primary human keratinocytes as experimental models, we have shown that UV irradiation (and other cellular stresses) activates TLR9 expression. This event is closely linked to p53 activation. Silencing the expression of p53 or deleting its encoding gene affected the activation of TLR9 expression after UV irradiation. Using various strategies, we have also shown that the transcription factors p53 and c-Jun are recruited onto a specific region of the TLR9 promoter after UV irradiation. Importantly, the E6 and E7 oncoproteins from beta HPV38, by inducing the accumulation of the p53 antagonist ΔNp73α, prevent the UV-mediated recruitment of these transcription factors onto the TLR9 promoter, with subsequent impairment of TLR9 gene expression. This study provides new insight into the mechanism that mediates TLR9 upregulation in response to cellular stresses. In addition, we show that HPV38 E6 and E7 are able to interfere with this mechanism, providing another explanation for the possible cooperation of beta HPV types with UV radiation in skin carcinogenesis.IMPORTANCE Beta HPV types have been suggested to act as cofactors in UV-induced skin carcinogenesis by altering several cellular mechanisms activated by UV radiation. We show that the expression of TLR9, a sensor of damage-associated molecular patterns produced during cellular stress, is activated by UV radiation in primary human keratinocytes (PHKs). Two transcription factors known to be activated by UV radiation, p53 and c-Jun, play key roles in UV-activated TLR9 expression. The E6 and E7 oncoproteins from beta HPV38 strongly inhibit UV-activated TLR9 expression by preventing the recruitment of p53 and c-Jun to the TLR9 promoter. Our findings provide additional support for the role that beta HPV types play in skin carcinogenesis by preventing activation of specific pathways upon exposure of PHKs to UV radiation.
journal_name
J Viroljournal_title
Journal of virologyauthors
Pacini L,Ceraolo MG,Venuti A,Melita G,Hasan UA,Accardi R,Tommasino Mdoi
10.1128/JVI.01123-17subject
Has Abstractpub_date
2017-09-12 00:00:00issue
19eissn
0022-538Xissn
1098-5514pii
JVI.01123-17journal_volume
91pub_type
杂志文章abstract::Interferons inhibit the replication of vesicular stomatitis virus (VSV), but not of encephalomyocarditis virus (EMCV), in mouse JLSV-11 cells. We report the isolation of clonal derivatives from this cell line in which the replication of both viruses is impaired by interferons. These clones were selected from the paren...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.62.9.3175-3181.1988
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abstract::HIV-1 causes a persistent infection of the immune system that is associated with chronic comorbidities. The mechanisms that underlie this inflammation are poorly understood. Emerging literature has implicated proinflammatory purinergic receptors and downstream signaling mediators in HIV-1 infection. This study probed ...
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journal_title:Journal of virology
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00125-09
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.54.2.483-492.1985
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.78.5.2627-2631.2004
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journal_title:Journal of virology
pub_type: 杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章
doi:10.1128/jvi.77.8.4950-4959.2003
更新日期:2003-04-01 00:00:00
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pub_type: 杂志文章
doi:10.1128/JVI.80.3.1130-1139.2006
更新日期:2006-02-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.72.7.5449-5456.1998
更新日期:1998-07-01 00:00:00
abstract::The N-terminal domain of the bovine papillomavirus type 1 E2 protein is important for viral DNA replication, for transcriptional transactivation, and for interaction with the E1 protein. To determine which residues of this 200-amino-acid domain are important for these activities, single conservative amino acid substit...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.70.1.23-29.1996
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.55.2.417-423.1985
更新日期:1985-08-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.9.4.664-671.1972
更新日期:1972-04-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.66.4.1899-1906.1992
更新日期:1992-04-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章
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更新日期:1996-06-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.06636-11
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00856-19
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00675-11
更新日期:2011-10-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.79.8.4640-4650.2005
更新日期:2005-04-01 00:00:00
abstract::Human immunodeficiency virus type 1 (HIV-1) entry into target cells requires folding of two heptad-repeat regions (N-HR and C-HR) of gp41 into a trimer of N-HR and C-HR hairpins, which brings viral and target cell membranes together to facilitate membrane fusion. Peptides corresponding to the N-HR and C-HR of gp41 are...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.77.3.1666-1671.2003
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abstract::Murine gammaherpesvirus 68 (MHV68) infection of mice provides a tractable small-animal system for assessing viral requirements for establishment of and reactivation from latency. The M2 gene product has no homology to any known proteins but has been shown to play a role in both the establishment of MHV68 latency and r...
journal_title:Journal of virology
pub_type: 杂志文章
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更新日期:2008-08-01 00:00:00
abstract::Human herpesvirus 8 (HHV8) open reading frame (ORF) 21 is predicted to encode a protein similar to the thymidine kinase (TK) enzyme of other herpesviruses. Expressed in mammalian cells, ORF 21 was found to have low TK activity, based on poor growth in media containing hypoxanthine-aminopterin-thymidine (HAT) and low i...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.74.2.684-692.2000
更新日期:2000-01-01 00:00:00
abstract::We established a system for propagation of Sindbis virus (SIN)-based replicons in tissue culture in the form of a tricomponent genome virus. Three RNA fragments containing complementing genetic information required for virus replication are packaged into separate viral particles, and each cell produces at least 1,000 ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.79.1.637-643.2005
更新日期:2005-01-01 00:00:00
abstract::Mammalian cells infected with human adenoviruses (Ads) undergo an apoptotic response as a result of expression of the viral E1A proteins, and this process is suppressed by the viral E1B-19K protein. The intermediary steps in the Ad-induced apoptosis pathway are not fully resolved. The apical step in the canonical mamm...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00808-07
更新日期:2007-10-01 00:00:00