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Pathway: The role of Nef in HIV-1 replication and disease pathogenesis

Authored: Gillespie, ME, 2007-07-25 19:42:36 more...

The HIV-1 Nef protein is a 27-kDa myristoylated protein that is abundantly produced during the early phase of viral replication cycle. It is highly conserved in all primate lentiviruses, suggesting that its function is essential for survival of these pathogens. The protein name "Nef" was derived from early reports of its negative effect on viral replication, thus 'negative factor' or Nef. Subsequently it has been demonstrated that Nef plays an important role in several steps of HIV replication. In addition, it appears to be a critical pathogenic factor, as Nef-deficient SIV and HIV are significantly less pathogenic than the wild-type viruses, whereas Nef-transgenic mice show many features characteristic to HIV disease.

The role of Nef in HIV-1 replication and disease pathogenesis is determined by at least four independent activities of this protein. Nef affects the cell surface expression of several cellular proteins, interferes with cellular signal transduction pathways, enhances virion infectivity and viral replication, and regulates cholesterol trafficking in HIV-infected cells.

Reviewed: Skowronski, J, 2007-08-07 14:33:41

References:

  • Differential effects of nef on HIV replication: implications for viral pathogenesis in the host Science 246:1629-32 [PubMed]
  • Nef harbors a major determinant of pathogenicity for an AIDS-like disease induced by HIV-1 in transgenic mice Cell 95:163-75 [PubMed]
  • Transgenic mice expressing human immunodeficiency virus type 1 in immune cells develop a severe AIDS-like disease J Virol 72:121-32 [PubMed]
  • Protective effects of a live attenuated SIV vaccine with a deletion in the nef gene Science 258:1938-41 [PubMed]
  • Live attenuated, nef-deleted SIV is pathogenic in most adult macaques after prolonged observation AIDS 17:157-66 [PubMed]
  • Nef protein of HIV-1 is a transcriptional repressor of HIV-1 LTR Science 241:1481-5 [PubMed]
  • Lymphoproliferative immune function in the Sydney Blood Bank Cohort, infected with natural nef/long terminal repeat mutants, and in other long-term survivors of transfusion-acquired HIV-1 infection AIDS 11:1565-74 [PubMed]
  • Roles of HIV-1 auxiliary proteins in viral pathogenesis and host-pathogen interactions Cell Res 15:923-34 [PubMed]

 

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