NF-kappaB activation and HIV-1 induced apoptosis

Cytokine Growth Factor Rev. Sep-Dec 1999;10(3-4):235-53. doi: 10.1016/s1359-6101(99)00015-5.

Abstract

HIV infection leads to the progressive loss of CD4+ T cells and the near complete destruction of the immune system in the majority of infected individuals. High levels of viral gene expression and replication result in part from the activation of NF-kappaB transcription factors, which in addition to orchestrating the host inflammatory response also activate the HIV-1 long terminal repeat. NF-kappaB induces the expression of numerous cytokine, chemokine, growth factor and immunoregulatory genes, many of which promote HIV-1 replication. Thus, NF-kappaB activation represents a double edged sword in HIV-1 infected cells, since stimuli that induce an NF-kappaB mediated immune response will also lead to enhanced HIV-1 transcription. NF-kappaB has also been implicated in apoptotic signaling, protecting cells from programmed cell death under most circumstances and accelerating apoptosis in others. Therefore, activation of NF-kappaB can impact upon HIV-1 replication and pathogenesis at many levels, making the relationship between HIV-1 expression and NF-kappaB activation multi-faceted. This review will attempt to analyse the many faces and functions of NF-kappaB in the HIV-1 lifecycle.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acquired Immunodeficiency Syndrome / physiopathology
  • Amino Acid Sequence
  • Animals
  • Apoptosis / physiology*
  • HIV Infections / pathology
  • HIV-1 / metabolism*
  • Humans
  • I-kappa B Kinase
  • I-kappa B Proteins / metabolism
  • Molecular Sequence Data
  • NF-kappa B / metabolism*
  • Protein-Serine-Threonine Kinases / metabolism
  • Signal Transduction
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • I-kappa B Proteins
  • NF-kappa B
  • Tumor Necrosis Factor-alpha
  • Protein-Serine-Threonine Kinases
  • CHUK protein, human
  • I-kappa B Kinase
  • IKBKB protein, human
  • IKBKE protein, human