The HLA class II transcriptional activator blocks the function of HIV-1 Tat and inhibits viral replication

Roberto S. Accolla, Stefania Mazza, Andrea De Lerma Barbaro, Andrea De Maria, Giovanna Tosi

Research output: Contribution to journalArticle

Abstract

The expression of HLA class II genes is under the control of a transcriptional activator, CIITA, encoded by the AIR-1 locus. Here we show that CIITA inhibits HIV-1 LTR transactivation mediated by Tat. The inhibition occurred when CIITA and Tat were transiently expressed in cells after transfection and, most importantly, when tat cDNA was transfected in cells expressing CIITA in a constitutive fashion and at physiological levels. Furthermore, CIITA inhibited the HIV-1 LTR transactivation mediated by extracellular Tat protein. CIITA inhibition of Tat function could be reversed by overexpression of Cyclin T1, the cellular cofactor used by Tat to facilitate elongation of viral transcripts. CIITA inhibition of Tat function had a dramatic effect on HIV-1 productive infection of human T cells because CIITA+ T cells supported very poorly, if any, viral replication. These results indicate that sustained expression of CIITA in HIV-1-susceptible targets may down-regulate viral expression both in cells actively replicating the virus and in silently infected cells requiring exogenous Tat to reactivate virus from latency.

Original languageEnglish
Pages (from-to)2783-2791
Number of pages9
JournalEuropean Journal of Immunology
Volume32
Issue number10
DOIs
Publication statusPublished - Oct 2002

Keywords

  • AIR-1
  • CIITA
  • Cyclin T1
  • HIV-1 replication
  • Tat

ASJC Scopus subject areas

  • Immunology

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