title: ISG15 expression correlates with HIV-1 viral load and with factors regulating T cell response.
abstract: Given the multifactorial nature of action of type I interferon (IFN) in HIV-1 infection and the need to firmly establish the action of key components of IFN pathways, we compared the IFN stimulated gene (ISG)15 expression with that of other well-characterized ISGs, evaluating its relationship with immunosuppressive factors regulating T-cell response in HIV-1 patients. PBMC from 225 subjects were included: healthy donors (n=30), naïve (n=93) and HAART treated HIV-1 subjects (n=102). Levels of ISG15-mRNA, ISG56-mRNA, APOBEC3G/3F-mRNA, TRAIL-mRNA, IDO-mRNA, proviral load andISG15 (rs15842 and rs1921) SNPs were evaluated by using TaqMan assays. We found that ISG15, ISG56, APOBEC3G/3F levels were increased in untreated HIV-1 patients compared to healthy donors, being ISG15 the highest ISG expressed. The amount of ISG15 correlated with viral load and with CD4+ T cell counts whereas no relationship was found between all ISGs analyzed and proviral load or HIV-1 tropism. ISG15 expression was reduced following long-term antiretroviral therapy. In addition, ISG15 levels were correlated with those of TRAIL and IDO in HIV-1 viremic patients. Lastly, ISG15 SNPs had no influence on ISG15 levels. We demonstrates that ISG15 is elevated in viremic HIV-1 patients and is associated with high TRAIL and IDO levels.
authors.affiliation: Pasteur Institute-Cenci Bolognetti Foundation, Department of Molecular Medicine, Laboratory of Virology, Sapienza University of Rome, Italy. Electronic address: carolina.scagnolari@uniroma1.it.
authors.forename: Carolina
authors.initials: C
authors.lastname: Scagnolari
authors.affiliation: Pasteur Institute-Cenci Bolognetti Foundation, Department of Molecular Medicine, Laboratory of Virology, Sapienza University of Rome, Italy. Electronic address: katia.monteleone@uniroma1.it.
authors.forename: Katia
authors.initials: K
authors.lastname: Monteleone
authors.affiliation: Pasteur Institute-Cenci Bolognetti Foundation, Department of Molecular Medicine, Laboratory of Virology, Sapienza University of Rome, Italy. Electronic address: carla.selvaggi@uniroma1.it.
authors.forename: Carla
authors.initials: C
authors.lastname: Selvaggi
authors.affiliation: Pasteur Institute-Cenci Bolognetti Foundation, Department of Molecular Medicine, Laboratory of Virology, Sapienza University of Rome, Italy. Electronic address: alessandra.pierangeli@uniroma1.it.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Pierangeli
authors.affiliation: Department of Public Health and Infectious Diseases, Sapienza University of Rome, Italy. Electronic address: gabriella.dettorre@uniroma1.it.
authors.forename: Gabriella
authors.initials: G
authors.lastname: D'Ettorre
authors.affiliation: Department of Clinical Medicine, Sapienza University of Rome, Italy. Electronic address: ivano.mezzaroma@uniroma1.it.
authors.forename: Ivano
authors.initials: I
authors.lastname: Mezzaroma
authors.affiliation: Pasteur Institute-Cenci Bolognetti Foundation, Department of Molecular Medicine, Laboratory of Virology, Sapienza University of Rome, Italy. Electronic address: ombretta.turriziani@uniroma1.it.
authors.forename: Ombretta
authors.initials: O
authors.lastname: Turriziani
authors.affiliation: Pasteur Institute-Cenci Bolognetti Foundation, Department of Molecular Medicine, Laboratory of Virology, Sapienza University of Rome, Italy. Electronic address: massimo.gentile@uniroma1.it.
authors.forename: Massimo
authors.initials: M
authors.lastname: Gentile
authors.affiliation: Department of Public Health and Infectious Diseases, Sapienza University of Rome, Italy. Electronic address: vincenzo.vullo@uniroma1.it.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Vullo
authors.affiliation: Pasteur Institute-Cenci Bolognetti Foundation, Department of Molecular Medicine, Laboratory of Virology, Sapienza University of Rome, Italy. Electronic address: carolina.scagnolari@uniroma1.it.
authors.forename: Guido
authors.initials: G
authors.lastname: Antonelli
mesh_terms: D000071480:APOBEC-3G Deaminase; D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D016022:Case-Control Studies; D003564:Cytidine Deaminase / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000235:genetics* / Q000276:immunology; D043525:Cytosine Deaminase / Q000235:genetics / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation; D015658:HIV Infections / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000276:immunology; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000235:genetics* / Q000276:immunology; D016601:RNA-Binding Proteins; D015398:Signal Transduction; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics* / Q000276:immunology; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology; D014452:Ubiquitins / Q000235:genetics* / Q000276:immunology; D019562:Viral Load / Q000187:drug effects; D056189:Viral Tropism; D014766:Viremia / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology / Q000821:virology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D016207:Cytokines; C576710:IDO1 protein, human; C484290:IFIT1 protein, human; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014157:Transcription Factors; D014452:Ubiquitins; C074034:ISG15 protein, human; C492906:APOBEC3F protein, human; D043525:Cytosine Deaminase; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase
keywords: APOBEC3F; APOBEC3G; HIV-1; IDO; IFN; ISG15; TRAIL