title: Circulating levels of miR-150 are associated with poorer outcomes of A/H1N1 infection.
abstract: BACKGROUND
  Overproduction of pro-inflammatory cytokines and chemokines is frequently associated with severe clinical manifestations in patients infected with influenza A/H1N1 virus. Micro-RNAs (miRNAs) are highly conserved small non-coding RNA molecules that post-transcriptionally regulate gene expression and are potential biomarkers and therapeutic targets in different inflammatory conditions.
  
  
  METHODS
  We studied the circulating and miRNA profiles in critically ill A/H1N1 patients, A/H1N1 patients with milder disease, asymptomatic housemates and healthy controls. Cytokine, chemokine and growth factors that were potential targets of differentially expressed miRNAs were assessed. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and interactome analysis of these miRNAs were also performed.
  
  
  RESULTS
  Critically ill patients exhibited a significant over-expression of circulating miR-150 (p<0.005) when compared to patients with milder disease. miR-29c, miR-145 and miR-22 were differentially expressed in patients with severe A/H1N1 disease whereas miR-210, miR-126 and miR-222 were downregulated in individuals exposed to the A/H1N1 virus. Significant correlations (p<0.05) between circulating levels of miR-150 with IL-1ra, IL-2, IL-6, CXCL8, IFN-γ, CXCL10 and G-CSF were detected, particularly in critically ill patients.
  
  
  CONCLUSIONS
  The up-regulation of miR-150 is associated with poorer outcomes of A/H1N1 infection. The differential expression of miRNAs related with immune processes in severe A/H1N1 disease supports the potential role of these miRNAs as biomarkers of disease progression.
authors.affiliation: Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico.
authors.forename: Juan
authors.initials: J
authors.lastname: Morán
authors.affiliation: Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico. Electronic address: grmunam@yahoo.com.mx.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Ramírez-Martínez
authors.affiliation: Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico.
authors.forename: Luis
authors.initials: L
authors.lastname: Jiménez-Alvarez
authors.affiliation: Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Cruz
authors.affiliation: Department of Infectious Diseases, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico.
authors.forename: Santiago
authors.initials: S
authors.lastname: Pérez-Patrigeon
authors.affiliation: Instituto Nacional de Medicina Genómica, Mexico City, Mexico.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Hidalgo
authors.affiliation: Instituto Nacional de Medicina Genómica, Mexico City, Mexico.
authors.forename: Lorena
authors.initials: L
authors.lastname: Orozco
authors.affiliation: Instituto Nacional de Medicina Genómica, Mexico City, Mexico.
authors.forename: Angélica
authors.initials: A
authors.lastname: Martínez
authors.affiliation: Department of Microbiology and Parasitology, Facultad de Medicina, Posgrado en Ciencias Biológicas, Universidad Nacional Autónoma de México, Mexico.
authors.forename: Luis
authors.initials: L
authors.lastname: Padilla-Noriega
authors.affiliation: FES-Iztacala, Unidad de Biomedicina, UBIMED, Universidad Nacional Autónoma de México, Mexico City, Mexico.
authors.forename: Federico
authors.initials: F
authors.lastname: Avila-Moreno
authors.affiliation: Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico.
authors.forename: Carlos
authors.initials: C
authors.lastname: Cabello
authors.affiliation: Department of Transplantation, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
authors.forename: Julio
authors.initials: J
authors.lastname: Granados
authors.affiliation: Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico.
authors.forename: Blanca
authors.initials: B
authors.lastname: Ortíz-Quintero
authors.affiliation: Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Ramírez-Venegas
authors.affiliation: Department of Infectious Diseases, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico.
authors.forename: Guillermo M
authors.initials: GM
authors.lastname: Ruíz-Palacios
authors.affiliation: Department of Biophysics and Physiology, University of California Irvine, CA, USA.
authors.forename: Albert
authors.initials: A
authors.lastname: Zlotnik
authors.affiliation: Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca City, Mexico.
authors.forename: Enrique
authors.initials: E
authors.lastname: Merino
authors.affiliation: Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico. Electronic address: joazu@yahoo.com.
authors.forename: Joaquín
authors.initials: J
authors.lastname: Zúñiga
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood*; D016022:Case-Control Studies; D002478:Cells, Cultured; D016207:Cytokines / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics*; D007251:Influenza, Human / Q000097:blood / Q000235:genetics* / Q000821:virology; D008297:Male; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; D016207:Cytokines; D035683:MicroRNAs; D012333:RNA, Messenger; C533097:MIR150, human
keywords: Circulating microRNAs; Critically ill patients; Influenza; Pandemic influenza A/H1N1; miR-150; miRNAs