title: Interleukin-32 isoforms: expression, interaction with interferon-regulated genes and clinical significance in chronically HIV-1-infected patients.
abstract: Given the growing evidence for a role of interleukin-32 (IL-32) in the immune response to HIV-1 infection and its interplay with type I and III interferons (IFNs), we studied the gene expression of IL-32 isoforms (α and nonα) in untreated chronically HIV-1-infected patients and in gender- and age-matched healthy individuals. To further characterize both the anti-HIV properties of IL-32 and the cytokine's relationship with host antiviral innate immune responses, we evaluated whether IL-32 can induce ex vivo the expression of antiviral IFN-induced genes (ISGs), namely myxovirus resistance A (MxA), and apolipoprotein B mRNA-editing enzyme catalytic (APOBEC)3G and APOBEC3F. We also investigated whether in vivo IL-32 (α and nonα) mRNA levels were correlated with those of MxA and APOBEC3G/3F. Results indicated that IL-32 (α and nonα) mRNA levels were significantly higher in HIV-1-infected patients than in healthy individuals. Furthermore, IL-32 (α and nonα) mRNA levels correlated negatively with HIV RNA levels, but not with the CD4(+) T-cell count. Our ex vivo studies disclosed that ISGs mRNA levels were increased after IL-32γ treatment of peripheral blood mononuclear cells. Interestingly, significant positive correlations were found between transcript levels of both IL-32α and IL-32nonα and those of MxA and APOBEC3G/3F in untreated chronically HIV-1-infected patients. Overall, our results demonstrated that IL-32 isoforms are highly expressed during chronic HIV-1 infection and that IL-32 could have a central role in the antiviral immune response against HIV-1.
authors.affiliation: Pasteur Institute-Cenci Bolognetti Foundation, Department of Molecular Medicine, Laboratory of Virology, Sapienza University of Rome, Viale di Porta Tiburtina n 28, 00185, Rome, Italy.
authors.forename: Katia
authors.initials: K
authors.lastname: Monteleone
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Di Maio
authors.forename: Giulia
authors.initials: G
authors.lastname: Cacciotti
authors.forename: Francesca
authors.initials: F
authors.lastname: Falasca
authors.forename: Maurizio
authors.initials: M
authors.lastname: Fraulo
authors.forename: Mario
authors.initials: M
authors.lastname: Falciano
authors.forename: Ivano
authors.initials: I
authors.lastname: Mezzaroma
authors.forename: Gabriella
authors.initials: G
authors.lastname: D'Ettorre
authors.forename: Ombretta
authors.initials: O
authors.lastname: Turriziani
authors.forename: Carolina
authors.initials: C
authors.lastname: Scagnolari
mesh_terms: D000071480:APOBEC-3G Deaminase; D000328:Adult; D002478:Cells, Cultured; D003564:Cytidine Deaminase / Q000096:biosynthesis*; D043525:Cytosine Deaminase / Q000096:biosynthesis*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology / Q000302:isolation & purification; D006801:Humans; D007378:Interleukins / Q000235:genetics / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008875:Middle Aged; D064547:Myxovirus Resistance Proteins / Q000096:biosynthesis*; D020033:Protein Isoforms / Q000235:genetics / Q000276:immunology*
chemical_list: C496971:IL32 protein, human; D007378:Interleukins; C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; D020033:Protein Isoforms; C492906:APOBEC3F protein, human; D043525:Cytosine Deaminase; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase