RESUMEN
The influenza virus (IV) triggers a series of signalling events inside host cells and induces complex cellular responses. Studies have suggested that host factors play an essential role in IV replication. MicroRNAs (miRNAs) represent a class of small non-coding RNAs that target mRNAs, triggering either translation repression or RNA degradation. Emerging research suggests that host-derived cellular miRNAs are involved in mediating the host-IV interaction. Using miRNA microarrays, we identified several miRNAs aberrantly expressed in IV-infected human lung epithelial cells (A549). Specifically, miR-let-7c was highly up-regulated in IV-infected A549 cells. PITA and miRanda database screening indicated that the let-7c seed sequence is a perfect complementary sequence match to the 3' untranslated region (UTR) of viral gene M1 (+) cRNA, but not to PB2 and PA. As detected by a luciferase reporter system, let-7c directly targeted the 3'-UTR of M1 (+) cRNA, but not PB2 and PA. To experimentally identify the function of cellular let-7c, precursor let-7c was transfected into A549 cells. Let-7c down-regulated IV M1 expression at both the (+) cRNA and protein levels. Furthermore, transfection with a let-7c inhibitor enhanced the expression of M1. Therefore, let-7c may reduce IV replication by degrading M1 (+) cRNA. This is the first report indicating that cellular miRNA regulates IV replication through the degradation of viral gene (+) cRNA by matching the 3'-UTR of the viral cRNA. These findings suggest that let-7c plays a role in protecting host cells from the virus in addition to its known cellular functions.
Asunto(s)
Células Epiteliales/virología , Subtipo H1N1 del Virus de la Influenza A/patogenicidad , Gripe Humana/virología , Pulmón/virología , MicroARNs/metabolismo , Proteínas de la Matriz Viral/metabolismo , Regiones no Traducidas 3' , Apoptosis , Línea Celular Tumoral , Supervivencia Celular , Biología Computacional , Regulación hacia Abajo , Células Epiteliales/citología , Interacciones Huésped-Patógeno , Humanos , Subtipo H1N1 del Virus de la Influenza A/fisiología , Gripe Humana/genética , Pulmón/citología , Pulmón/metabolismo , MicroARNs/genética , Análisis por Micromatrices , ARN Mensajero , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Regulación hacia Arriba , Replicación ViralRESUMEN
Human bocavirus, which was firstly discovered in 2005, is a new human parvovirus associated with lower respiratory tract infection in children. In this study, a human bocavirus, named WLL-1 isolate, was identified in Wenlin County, Zhejiang Province. The genome of bocavirus WLL-1 has been sequenced and analyzed. Phylogenetic analyses showed that WLL-1 shares 99% homology with other bocaviruses recently reported, but also has some special variations.