Circulating levels of miR-150 and miR-126 are associated with poor outcomes of influenza A/H1N1 virus infection

Background: miRNAs regulates antiviral immunity but their role as markers of severity or fatal outcome in influenza virus infections is unknown. Objective: To determine the role of miR-150 and miR-126 in the pathogenesis of severe pneumonia in humans and mice. Methods: Patients with A/H1N1 virus infection from the intensive care unit were studied; Group 1: patients surviving infection (N=15) and Group 2: patients with fatal outcome (N=17). Two samples of peripheral blood were obtained, one at the entrance of the ICU and another at the outcome. RNA was isolated and expression of miR-126 was quantified by qPCR. C57BL/6 wild type and miR-126 deficient mice were infected with A/H1N1 virus. Levels of cytokines and chemokines were assessed by Luminex. Differences were analyzed by Mann-Whitney U test. Results. Patients with fatal outcome were older than survivors (51 years±11 vs 41 years±9, p<0.05), higher mortality was observed in males (p<0.05). Higher levels of miR-150 were detected in both samples (initial and outcome) of patients who died in relation to surviving patients (p=0.01). Low levels of miR-126 were detected in both samples of patients with fatal outcome (p=0.04). Survivors had a low expression of miR-126. miR-126 deficient mice have impaired type I IFN responses against A/H1N1 virus, resulting in higher mortality and immunopathology in lung. Conclusion. High miR-150 and downregulated miR-126 expression are associated with poor outcomes A/H1N1 infection. miR-126 deficient mice have impaired antiviral responses against this strain. These miRNAs could be useful as indicators of poor outcomes and as therapeutic targets in influenza infection.