title: Decreased type I interferon receptor-soluble isoform in antiretroviral-treated HIV-positive children.
abstract: We developed a real-time PCR assay to simultaneously measure the mRNA level of type I interferon (IFN) receptor (IFNAR) components in peripheral blood cells of children with chronic immune stimulation due to HIV infection. All patients were undergoing antiretroviral therapy and were divided into two groups on the basis of the induction of MxA mRNA, a marker of type I IFN bioactivity. We found that IFNAR-2 subunit mRNA was higher than that of the IFNAR-1 subunit, that the mRNA for the IFNAR-2.2 functional isoform was more expressed than that for the truncated IFNAR-2.1 isoform, and both were much more represented than that of the IFNAR-2.3 soluble isoform. We also demonstrated that soluble isoform mRNA was significantly diminished in the subgroup of patients with MxA mRNA below the cutoff value (determined as the 99th percentile of MxA measured in healthy controls). These results suggest that downregulation of the soluble receptor isoform, which would not compete with the functional isoform for binding to the target cytokine, would give type I IFN, eventually induced in these patients in the case of viral reactivation, the opportunity to promptly exert its antiviral activity.
authors.affiliation: Laboratorio di Biotecnologie, Department of Diagnostics, Spedali Civili di Brescia, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Sottini
authors.forename: Claudia
authors.initials: C
authors.lastname: Ghidini
authors.forename: Federico
authors.initials: F
authors.lastname: Serana
authors.forename: Marco
authors.initials: M
authors.lastname: Chiarini
authors.forename: Monica
authors.initials: M
authors.lastname: Valotti
authors.forename: Raffaele
authors.initials: R
authors.lastname: Badolato
authors.forename: Annalisa
authors.initials: A
authors.lastname: Radeghieri
authors.forename: Luigi
authors.initials: L
authors.lastname: Caimi
authors.forename: Luisa
authors.initials: L
authors.lastname: Imberti
mesh_terms: D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D045744:Cell Line, Tumor; D002648:Child; D002675:Child, Preschool; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007370:Interferon Type I / Q000276:immunology / Q000378:metabolism; D008297:Male; D020033:Protein Isoforms / Q000097:blood* / Q000276:immunology; D012333:RNA, Messenger / Q000097:blood; D053633:Receptor, Interferon alpha-beta / Q000097:blood* / Q000235:genetics / Q000276:immunology
chemical_list: D019380:Anti-HIV Agents; D007370:Interferon Type I; D020033:Protein Isoforms; D012333:RNA, Messenger; D053633:Receptor, Interferon alpha-beta