HIV-1, NFAT, and cyclosporin: Immunosuppression for the immunosuppressed?

Academic Article

Abstract

  • The human immunodeficiency virus-1 (HIV-1), the cause of AIDS, remains a significant cause of morbidity and mortality throughout the planet. Although reverse transcriptase and protease inhibitors have substantially slowed the virus, viral resistance complicates therapy. Because HIV-1 relies on its host's transcriptional machinery for its own replication, strategies for targeting activation-dependent transcription factors in CD4 T cells are being considered for adjunctive therapy in HIV-1-infected individuals. The nuclear factor of activated T cells (NFAT) family of transcription factors is one such target. On T-cell stimulation, NFAT proteins translocate to the nucleus, where they activate a large number of early response genes, including cytokines such as interleukin-2. Activation and nuclear translocation of NFAT proteins are abrogated by the powerful immunosuppressants cyclosporin A (CsA) and FK506. Over the last several years, various investigators have demonstrated that NFAT proteins bind to the HIV-1 LTR promoter and increase viral transcription. In this report, further evidence supporting a role for NFAT proteins in augmenting HIV-1 transcription is presented. In addition, other mechanisms of HIV-1 inhibition by CsA are reviewed, and the rationale for the use of CsA to treat AIDS is discussed.
  • Digital Object Identifier (doi)

    Author List

  • Cron RQ
  • Start Page

  • 761
  • End Page

  • 767
  • Volume

  • 20
  • Issue

  • 12