Circulating MicroRNA Levels In Patients With Different clinical outcomes of The infection with influenza A/H1N1 Virus
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1
Instituto Nacional de Enfermedades Respiratorias "Ismael Coso Villegas", Inmunologia, Mexico
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2
Universidad Nacional Autónoma de México, Posgrado en Ciencias Biológicas, Mexico
RATIONALE. Current evidence suggests that the development of severe pneumonia in patients with pandemic (pdm) A/H1N1 infection is associated with an excessive immune activation. High levels of pro-inflammatory mediators have been detected in blood and lung from patients with pdm A/H1N1 infection. Even though cytokines, chemokines, and growth factors are required to control influenza virus infection, their overproduction in an uncontrolled inflammatory response can lead to lung tissue damage. MicroRNAs (miRNAs) regulate most of the cellular processes including antiviral inflammatory responses. The profiles of circulating miRNAs in patients with severe pneumonia associated to pdm A/H1N1 virus have not been described. METHODS. We analyzed the genome-wide circulating miRNA profile by RT-PCR in 29 individuals (8 with diagnosis of severe pneumonia by A/H1N1 virus, 8 with mild pneumonia by A/H1N1, 8 household asymptomatic contacts and 5 healthy controls). Total circulating RNA was extracted from a serum volume of 250μL using Trizol. TaqMan miRNA low-density arrays (TLDAs) covering 768 miRNA species and endogenous controls were used for miRNA profiling in all the individuals. miRNA TLDAs microarray data analyses were performed with an algorithm designed in Perl language. We performed standard normalization using U6 endogenous control. ANOVA and Mann Whitney tests were performed to analyze differences between groups. RESULTS. We found a set of circulating miRNAs that were differentially expressed (p<0.05) in the group of patients with A/H1N1 severe pneumonia (miR-150, 29c, miR-22). In other side miR-210 and miR-145 were marking the symptomatic form of the infection without a distinction between severity and non-severity of the included patients. Interestingly, we found a diminished expression of miR-126 and miR-222 at all the patients that were exposed to (pdm) A/H1N1 virus independently from the clinical outcome of the disease. KEEG pathways enrichment and interactome network (Cytoscape V3.1.1) analysis of the differentially expressed miRNAs in A/H1N1 infection shows a connection between miR29c, miR150, miR-210, miR-145, miR-222 and miR-126 networking principally with the (PI3K)-Akt-mTOR, VEGF, Cancer and antiviral pathways. CONCLUSIONS. The expression of circulating miRNAs is altered in patients with different clinical outcomes of A/H1N1 infection. To our knowledge, this is the first evidence of deregulated miRNA expression in severe A/H1N1 disease, providing insights that may lead to the identification of novel biomarkers and altered molecular pathways of the disease.
Keywords:
miRNAs,
H1N1pdm,
Pneumonia,
Cytokines,
TLDAs
Conference:
IMMUNOCOLOMBIA2015 - 11th Congress of the Latin American Association of Immunology - 10o. Congreso de la Asociación Colombiana de Alergia, Asma e Inmunología, Medellin, Colombia, 13 Oct - 16 Oct, 2015.
Presentation Type:
Oral Presentation
Topic:
Immunogenetics
Citation:
Moran
J,
Cruz-Lagunas
A,
Jimenez-Alvarez
LA,
Ramirez-Martinez
G and
Zúñiga
J
(2015). Circulating MicroRNA Levels In Patients With Different clinical outcomes of The infection with influenza A/H1N1 Virus.
Front. Immunol.
Conference Abstract:
IMMUNOCOLOMBIA2015 - 11th Congress of the Latin American Association of Immunology - 10o. Congreso de la Asociación Colombiana de Alergia, Asma e Inmunología.
doi: 10.3389/conf.fimmu.2015.05.00304
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Received:
15 May 2015;
Published Online:
15 Sep 2015.
*
Correspondence:
PhD. Joaquin Zúñiga, Instituto Nacional de Enfermedades Respiratorias "Ismael Coso Villegas", Inmunologia, Mexico City, 14080, Mexico, joazu@yahoo.com