Linked Life Data

17312167

Source:http://linkedlifedata.com/resource/pubmed/id/17312167

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2007-2-21
pubmed:abstractText
Cervical cancer development is linked to the persistent infection by high-risk mucosal human papillomaviruses (HPVs) types. The E6 and E7 major oncoproteins from this dsDNA virus play a key role in the deregulation of the cell cycle, apoptosis, and adaptive immune surveillance. In this study, we show for the first time that HPV type 16 (HPV16), the most carcinogenic type among the high-risk subgroup, interferes with innate immunity by affecting the expression of TLRs. Infection of human primary keratinocytes with HPV16 E6 and E7 recombinant retroviruses inhibits TLR9 transcription and hence functional loss of TLR9-regulated pathways. Similar findings were achieved in HPV16-positive cancer-derived cell lines and primary cervical cancers, demonstrating that this event occurs also in an in vivo context. Interestingly, E6 and E7 from the low-risk HPV type 6 are unable to down-regulate the TLR9 promoter. In addition, E6 and E7 from the high-risk HPV type 18, which are known to persist less competently in the host than HPV16, have reduced efficiency compared with HPV16 in inhibiting TLR9 transcription. Furthermore, a CpG motif derived from the HPV16 E6 DNA sequence activated TLR9, indicating this virus is able to initiate innate responses via the receptor it later down-regulates. This study reveals a novel mechanism used by HPV16 to suppress the host immune response by deregulating the TLR9 transcript, providing evidence that abolishing innate responses may be a crucial step involved in the carcinogenic events mediated by HPVs.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
178
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3186-97
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
TLR9 expression and function is abolished by the cervical cancer-associated human papillomavirus type 16.
pubmed:affiliation
International Agency for Research on Cancer-World Health Organization, 150 Cours Albert-Thomas, 69372 Lyon Cedex 08, France. hasan@iarc.fr
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't