Constitutive activation of STATs upon in vivo human immunodeficiency virusinfection

Infection by the human immunodeficiency virus (HIV) either upregulates or d ownregulates the expression of several cytokines and interferons (IFNs) tha t use the Janus kinase/signal transducer and activator of transcription (JA K/STAT) pathway for signal transduction. However, very little is known on t he state of activation of the JAK/STAT pathway after HIV infection either i n vivo or in vitro. In this regard, we report here that a constitutive acti vation of a C-terminal truncated STAT5 (STAT5 Delta) and of STAT1 alpha occ urs in the majority (similar to 75%) of individuals with progressive HIV di sease. We have further demonstrated that, among peripheral blood mononuclea r cells (PBMCs), STAT5 Delta is activated preferentially in CD4(+) T cells. In contrast to a published report, expression of STATs from PBMCs of infec ted individuals was comparable with that of seronegative donors. In additio n, in vitro infection of mitogen-activated PBMCs with a panel of laboratory -adapted and primary HIV strains characterized by differential usage of che mokine coreceptors did not affect STAT protein levels. However, enhanced ac tivation of STAT was observed after in vitro infection of resting PBMCs and nonadherent PBMCs by different viral strains. Thus, constitutive STAT acti vation in CD4(+) T lymphocytes represents a novel finding of interest also as a potential new marker of immunological reconstitution of HIV-infected i ndividuals. (C) 1999 by The American Society of Hematology.