- 作者: Syed Shaheduzzaman, Vyjayanthi Krishnan, Ana Petrovic, Michael Bittner, Paul Meltzer, Jeffrey Trent, Sundararaian Venkatesan Steven Zeichnera
- 作者服務機構: HIV and AIDS Malignancy Branch, National Cancer lnstitute, Laboratory of Molecular Microbiology National Institute of Allergy and Infectious Diseases, Cancer Genetics Branch, Nationai Human Genome Research Institute, National institutes of Health, Bethesda, Md., USA
- 中文摘要: --
- 英文摘要: we identified several cellular genes whose expressionwas modulated differentially by Nef and its mutants. Weconfirmed the differential expression of selected genesby RNA filter blotting. Genes expressed at higher levelsincluded proteases, transcription factors, protein ki-nases, nuclear import/export proteins, adaptor mole-cules and cyclins, some of which have previously beenimplicated as being important for HIV replication andpathogenesis. The results indicate that Nef expressioncan alter the expression of cellular genes and suggestthat this alteration in cellular gene expression may serveto optimize the cell to support the subsequent stages ofviral replication.The early human immunodeficiency virus (HIV) accesso-ry protein Nef makes an important contribution to viru-lence, but the mechanisms by which Nef influencespathogenesis remain unclear. Many well-studied effectsof Nef, like CD4 and class I MHC downregulation,occurposttranslationally. However, Nef has the potential toaffect gene expression by interfering with cell signalingpathways and by virtue of structural features such as thePro-X-X-Pro motif, which may interact with src homolo-gy region-3 domains of src-like kinases. We used a cDNAmicroarray screening strategy to identify cellular geneswhose steady state transcriptional levels may be af-fected by Nef. We generated HeLa cell lines expressingwild-type or mutant HIV-1 nef protein sequences. UsingcDNA microarray technology, we compared the patternsof cellular gene expression in the various cell lines to thepattern in non-Nef-expressing HeLa cells. By matchingthe patterns of cellular gene expression in HeLa cell linesexpressing various Nefs with that of parental HeLa cells,
- 中文關鍵字: --
- 英文關鍵字: HIV, Nef, Microarray, Viral pathogenesis