title: Expression levels of the innate response gene RIG-I and its regulators RNF125 and TRIM25 in HIV-1-infected adult and pediatric individuals.
abstract: OBJECTIVE
  TLRs (Toll-like receptors) and RLRs (RIG-I-like receptors) mediate innate immune responses by detecting microorganism invasion. RIG-I activation results in the production of interferon (IFN) type 1 and IFN responsive genes (ISGs). As the ubiquitin ligases RNF125 and TRIM25 are involved in regulating RIG-I function, our aim was to assess whether the levels of these three genes vary between healthy and HIV-infected individuals and whether these levels are related to disease progression.
  
  
  METHODS
  Gene expression analyses for RIG-I, RNF125, and TRIM25 were performed for HIV-infected adults and the children's peripheral blood mononuclear cells (PBMCs).
  
  
  METHODS
  Reverse transcription-quantitative PCRs (RT-qPCRs) were performed in order to quantify the expression levels of RIG-I, RNF125 and TRIM25 from PBMCs purified from control or HIV-infected individuals.
  
  
  RESULTS
  Controls express higher levels of the three genes when compared to HIV-infected patients. These expressions are clearly distinct between healthy and progressors, and are reproduced in adults and children. In controls, RNF125 is the highest expressed gene, whereas in progressors, RIG-I is either the highest expressed gene or is expressed similarly to RNF125 and TRIM25.
  
  
  CONCLUSIONS
  A pattern of expression of RIG-I, RNF125, and TRIM25 genes in HIV patients is evident. The high expression of RNF125 in healthy individuals reflects the importance of keeping RIG-I function off, inhibiting unnecessary IFN production. Consistent with this assumption, RNF125 levels are lower in HIV patients and importantly, the RNF125/RIG-I ratio is lower in patients who progress to AIDS. Our results might help to predict disease progression and unveil the role of poorly characterized host genes during HIV infection.
authors.affiliation: aDepartamento de Genética, Instituto de Biologia bInstituto de Bioquímica Médica, UFRJ, Rio de Janeiro cFaculdade de Medicina, UFRG, Rio Grande dHospital Universitário Gaffrée e Guinle, UNIRIO eInstituto de Puericultura e Pediatria Martagão Gesteira, UFRJ fPrograma de Genética, INCA, Rio de Janeiro, Brazil.
authors.forename: Alan M A
authors.initials: AM
authors.lastname: Britto
authors.forename: Nívea D
authors.initials: ND
authors.lastname: Amoedo
authors.forename: Paula
authors.initials: P
authors.lastname: Pezzuto
authors.forename: Adriana O
authors.initials: AO
authors.lastname: Afonso
authors.forename: Ana M B
authors.initials: AM
authors.lastname: Martínez
authors.forename: Jussara
authors.initials: J
authors.lastname: Silveira
authors.forename: Fernando S
authors.initials: FS
authors.lastname: Sion
authors.forename: Elizabeth S
authors.initials: ES
authors.lastname: Machado
authors.forename: Marcelo A
authors.initials: MA
authors.lastname: Soares
authors.forename: Ana L M
authors.initials: AL
authors.lastname: Giannini
mesh_terms: D000293:Adolescent; D000328:Adult; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000096:biosynthesis*; D005260:Female; D020869:Gene Expression Profiling; D015658:HIV Infections / Q000473:pathology* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D007223:Infant; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D011971:Receptors, Immunologic; D014157:Transcription Factors / Q000096:biosynthesis*; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases / Q000096:biosynthesis*; D055815:Young Adult
chemical_list: D011971:Receptors, Immunologic; D014157:Transcription Factors; D000070584:Tripartite Motif Proteins; C551868:RNF125 protein, human; C084523:TRIM25 protein, human; D044767:Ubiquitin-Protein Ligases; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases