Address for correspondence: Dr. Mauro Piacentini, Laboratory of Cell Biology and Electronic Microscopy, "Lazzaro Spallanzani"—IRCCS, Via Portuense, 292, 00149 Rome, Italy. Voice: (39) 6 55 170 429.
mauro.piacentini{at}uniroma2.it
The cytopathic effect of HIV has been shown to be associated
with the induction of apoptosis and the inhibition of proliferation
of T cells. However, the cellular and molecular mechanisms at
the basis of the dramatic immune cell loss caused by HIV in
patients suffering from acquired immunodeficient syndrome (AIDS),
are not yet fully established. We demonstrated that "tissue"
transglutaminase (tTG) gene expression is induced in the immune
system of seropositive individuals (peripheral blood mononuclear
cells and lymph nodes). tTG is a multifunctional protein involved
in a variety of fundamentally important cellular functions,
in addition to cell death by apoptosis. The presence of high
tTG levels in immune-competent cells of HIV
+ persons might exert
an important role in HIV-infection by influencing viral production.
We propose that, in addition to its multiple functions, tTG
might interfere with HIV replication by altering the viral mRNA
trafficking between the nucleus and the cytoplasm. This effect
might be due to its specific interaction with eIF5A, a cellular
partner of HIV Rev protein, which is essential for HIV replication
in immune-competent cells. Given the presence of high tTG levels
in HIV
+ individuals, it would be of interest to pursue the potential
role of this multifunctional protein in the development of strategies
aimed at the pharmacologic regulation of HIV production.
