Global effects of human papillomavirus type 18 E6/E7 in an organotypic keratinocyte culture system.

Abstract:

:The effects of human papillomavirus type 18 (HPV-18) E6 and E7 proteins on global patterns of host gene expression in primary human keratinocytes grown in organotypic raft culture system were assessed. Primary human keratinocytes were infected with retroviruses that express the wild-type HPV-18 E6 and E7 genes from the native differentiation-dependent HPV enhancer-promoter. Total RNA was isolated from raft cultures and used to generate probes for querying Affymetrix U95A microarrays, which contain >12,500 human gene sequences. Quadruplicate arrays of each E6/E7-transduced and empty vector-transduced samples were analyzed by 16 pairwise comparisons. Transcripts altered in > or =12 comparisons were selected for further analysis. With this approach, HPV-18 E6/E7 expression significantly altered the expression of 1,381 genes. A large increase in transcripts associated with DNA and RNA metabolism was observed, with major increases noted for transcription factors, splicing factors, and DNA replication elements, among others. Multiple genes associated with protein translation were downregulated. In addition, major alterations were found in transcripts associated with the cell cycle and cell differentiation. Our study provides a systematic description of transcript changes brought about by HPV-18 E6/E7 in a physiologically relevant model and should furnish a solid source of information to guide future studies.

journal_name

J Virol

journal_title

Journal of virology

authors

Garner-Hamrick PA,Fostel JM,Chien WM,Banerjee NS,Chow LT,Broker TR,Fisher C

doi

10.1128/JVI.78.17.9041-9050.2004

subject

Has Abstract

pub_date

2004-09-01 00:00:00

pages

9041-50

issue

17

eissn

0022-538X

issn

1098-5514

pii

78/17/9041

journal_volume

78

pub_type

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