Visit our Expo - Redox and Inflammation signaling 2012

Session XIV : Transcriptional and translational control Poster XIV, 66
IRF-7: new role in the regulation of genes involved in the adaptive immunity
Marco Sgarbanti, Giulia Marsili, Anna Lisa Remoli, Roberto Orsatti
and Angela Battistini
Department of infectious, Parasitic and immunomediated Diseases, Istituto Superiore di
Sanità, viale Regina Elena, 299-Rome 00161, Italy. E-mail: battist@iss.it
The interferon regulatory factor 7 (IRF-7) a member of the IRF family of transcription factors
is a key player in the innate immune response against viral infections. Constitutive expression
of IRF-7 is limited to peripheral blood lymphocytes and dendritic cells while in other cell
types its expression can be induced by type I Interferon. IRF-7 is sequestered in the cytoplasm
of uninfected cells and following viral infection, double stranded RNA (dsRNA) or Toll-like
receptor (TLR) signalling it becames phosphorylated by TBK and IKK-i kinases.
Phosphorylated IRF-7 migrates in the nucleus where it can activate IFN-alpha genes and other
Interferon stimulated genes (ISGs). Here we report that the over-expression of a constitutively
active form of IRF-7 positively regulates the promoter of Interferon regulatory factor 1 (IRF-
1) and of the latent membrane protein 2 (LMP-2), two proteins, which play an important role
in adaptive immunity. We previously showed that in T cells, the HIV-1 trans-activator Tat
protein is able to modulate the expression of LMP2 through regulation of IRF-1 expression.
Experiments are, therefore, ongoing to determine whether the up-regulated expression of IRF-
1 and LMP-2 is mediated by the Tat-induced IRF-7 activation through the engagement of
TBK-1 and IKK-i kinases. Our data point to IRF-7 as a mediator that bridges innate and
adaptive immunity and a potential target of the HIV-1 Tat-mediated immune-modulation.
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