Journal of Biomedical Science

, Volume 9, Issue 1, pp 82–96

Effects of HIV-1 nef on cellular gene expression profiles

  • Syed Shaheduzzaman
  • Vyjayanthi Krishnan
  • Ana Petrovic
  • Michael Bittner
  • Paul Meltzer
  • Jeffrey Trent
  • Sundararajan Venkatesan
  • Steven Zeichner
Original Paper

DOI: 10.1007/BF02256581

Cite this article as:
Shaheduzzaman, S., Krishnan, V., Petrovic, A. et al. J Biomed Sci (2002) 9: 82. doi:10.1007/BF02256581

Abstract

The early human immunodeficiency virus (HIV) accessory protein Nef makes an important contribution to virulence, but the mechanisms by which Nef influences pathogenesis remain unclear. Many well-studied effects of Nef, like CD4 and class I MHC downregulation, occur posttranslationally. However, Nef has the potential to affect gene expression by interfering with cell signaling pathways and by virtue of structural features such as the Pro-X-X-Pro motif, which may interact withsrc homology region-3 domains of src-like kinases. We used a cDNA microarray screening strategy to identify cellular genes whose steady state transcriptional levels may be affected by Nef. We generated HeLa cell lines expressing wild-type or mutant HIV-1nef protein sequences. Using cDNA microarray technology, we compared the patterns of cellular gene expression in the various cell lines to the pattern in non-Nef-expressing HeLa cells. By matching the patterns of cellular gene expression in HeLa cell lines expressing various Nefs with that of parental HeLa cells, we identified several cellular genes whose expression was modulated differentially by Nef and its mutants. We confirmed the differential expression of selected genes by RNA filter blotting. Genes expressed at higher levels included proteases, transcription factors, protein kinases, nuclear import/export proteins, adaptor molecules and cyclins, some of which have previously been implicated as being important for HIV replication and pathogenesis. The results indicate that Nef expression can alter the expression of cellular genes and suggest that this alteration in cellular gene expression may serve to optimize the cell to support the subsequent stages of viral replication.

Key Words

HIVNefMicroarrayViral pathogenesis

Copyright information

© National Science Council 2002

Authors and Affiliations

  • Syed Shaheduzzaman
    • 3
  • Vyjayanthi Krishnan
    • 3
  • Ana Petrovic
    • 1
  • Michael Bittner
    • 2
  • Paul Meltzer
    • 2
  • Jeffrey Trent
    • 2
  • Sundararajan Venkatesan
    • 1
  • Steven Zeichner
    • 3
  1. 1.Laboratory of Molecular MicrobiologyNational Institute of Allergy and Infectious DiseasesUSA
  2. 2.Cancer Genetics BranchNational Human Genome Research Institute, National Institutes of HealthBethesdaUSA
  3. 3.10S255, Building 10, HAMB, NCI, NIHBethesdaUSA