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.
Keywords:
APOBEC3F; APOBEC3G; HIV-1; IDO; IFN; ISG15; TRAIL.
Copyright © 2015 Elsevier GmbH. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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APOBEC-3G Deaminase
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Adaptor Proteins, Signal Transducing
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Adult
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Antiretroviral Therapy, Highly Active
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CD4 Lymphocyte Count
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CD4-Positive T-Lymphocytes / immunology*
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CD4-Positive T-Lymphocytes / virology
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Case-Control Studies
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Cytidine Deaminase / genetics
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Cytidine Deaminase / immunology
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Cytokines / genetics*
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Cytokines / immunology
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Cytosine Deaminase / genetics
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Cytosine Deaminase / immunology
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Female
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Gene Expression Regulation
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HIV Infections / drug therapy
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HIV Infections / genetics*
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HIV Infections / immunology
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HIV Infections / virology
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HIV-1 / drug effects
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HIV-1 / immunology
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Humans
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Indoleamine-Pyrrole 2,3,-Dioxygenase / genetics*
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Indoleamine-Pyrrole 2,3,-Dioxygenase / immunology
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Male
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Middle Aged
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Polymorphism, Single Nucleotide
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RNA, Messenger / genetics*
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RNA, Messenger / immunology
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RNA-Binding Proteins
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Signal Transduction
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TNF-Related Apoptosis-Inducing Ligand / genetics*
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TNF-Related Apoptosis-Inducing Ligand / immunology
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Transcription Factors / genetics
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Transcription Factors / immunology
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Ubiquitins / genetics*
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Ubiquitins / immunology
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Viral Load / drug effects
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Viral Tropism
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Viremia / drug therapy
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Viremia / genetics*
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Viremia / immunology
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Viremia / virology
Substances
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Adaptor Proteins, Signal Transducing
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Cytokines
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IDO1 protein, human
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IFIT1 protein, human
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Indoleamine-Pyrrole 2,3,-Dioxygenase
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RNA, Messenger
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RNA-Binding Proteins
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TNF-Related Apoptosis-Inducing Ligand
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TNFSF10 protein, human
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Transcription Factors
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Ubiquitins
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ISG15 protein, human
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APOBEC3F protein, human
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Cytosine Deaminase
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APOBEC-3G Deaminase
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APOBEC3G protein, human
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Cytidine Deaminase