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Blood, Vol. 94 No. 12 (December 15), 1999:
pp. 4202-4209
Constitutive Activation of STATs Upon In Vivo Human
Immunodeficiency Virus Infection
Chiara Bovolenta,
Laura Camorali,
Alessandro L. Lorini,
Silvia Ghezzi,
Elisa Vicenzi,
Adriano Lazzarin, and
Guido Poli
From the AIDS Immunophatogenesis Unit, DIBIT, and the Division of
Infectious Diseases, Centro San Luigi, San Raffaele Scientific
Institute, Milan, Italy.
Infection by the human immunodeficiency virus (HIV) either
upregulates or downregulates the expression of several cytokines and
interferons (IFNs) that use the Janus kinase/signal transducer and
activator of transcription (JAK/STAT) pathway for signal transduction. However, very little is known on the state of activation of the JAK/STAT pathway after HIV infection either in vivo or in vitro. In
this regard, we report here that a constitutive activation of a
C-terminal truncated STAT5 (STAT5 ) and of STAT1 occurs in the
majority (~75%) of individuals with progressive HIV disease. We have
further demonstrated that, among peripheral blood mononuclear cells
(PBMCs), STAT5 is activated preferentially in CD4+ T
cells. In contrast to a published report, expression of STATs from
PBMCs of infected individuals was comparable with that of seronegative
donors. In addition, in vitro infection of mitogen-activated PBMCs with
a panel of laboratory-adapted and primary HIV strains characterized by
differential usage of chemokine coreceptors did not affect STAT protein
levels. However, enhanced activation of STAT was observed after in
vitro infection of resting PBMCs and nonadherent PBMCs by different
viral strains. Thus, constitutive STAT activation in CD4+
T lymphocytes represents a novel finding of interest also as a
potential new marker of immunological reconstitution of HIV-infected individuals.
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