Project description:This series includes 1 microarray used to detect a human metapneumovirus strain associated with critical respiratory illness in an elderly male with leukemia (Chiu, et al 2006) Keywords: viral detection
Project description:Human metapneumovirus (HMPV) is a primary causative agent of acute lower respiratory tract infections. We used single cell RNA-sequencing (scRNA-seq) to assess lung immune profiles in a mouse model of HMPV infection.
Project description:Human metapneumovirus (HMPV) is a primary causative agent of acute upper respiratory tract infections. We used single cell RNA-sequencing (scRNA-seq) to assess nasal immune profiles in a mouse model of HMPV infection.
Project description:In vitro infection experiment with genetically modified human metapneumovirus (HMPV) to study the function of the viral small hydrophobic (SH) protein.
Project description:Background. Human Metapneumovirus (HMPV) and Respiratory Syncytial Virus (RSV), are responsible for respiratory diseases mostly in children. In spite of the resemblance between these two pneumoviruses, they elicit a different extent of immune response. miRNAs are small non coding RNAs that regulate gene expression and are involved in numerous cellular processes including the immune system. Methodology. Human monocyte-derived dendritic cells (moDC) were differentiated from peripheral blood mononuclear cells and infected at an MOI of 3 for 24h. RNA was isolated to analyze the miRNAs transcription by high throughput sequencing using illumina technology. Principal findings. Infection with HMPV up-regulated the expression of hsa-miR-4448, while RSV infection induced significant expression of hsa-miR-30a-5p, hsa-miR-182-5p, hsa-miR-1913, hsa37, miR-4448 and hsa-miR-4634. Conclusions/Significance. In human monocyte derived dendritic cells (moDC), RSV and HMPV induced different profiles of miRNA expression. Understanding the changes of miRNA expression profiles by RSV and HMPV in immune cells will further our understanding of the differential immune response induced by these respiratory viruses
Project description:N6-methyladenosine (m6A) is a widespread mRNA modification that regulates RNA metabolism and influences virus-induced immune responses. We performed MeRIP-seq to profile m6A landscapes in THP-1-derived immature dendritic cells (THP-iDCs) before and after infection with Human metapneumovirus (hMPV, NL/00/1) or mumps virus (MuV, JL2). Integration of m6A modifications on key innate immune transcripts with transcriptomic data, together with m6A levels on cellular and viral RNA, revealed a dual role of m6A in viral replication and host immune regulation. These datasets provide a resource for exploring epitranscriptomic regulation during hMPV and MuV infection.
Project description:Tissue resident memory cells are long-lived sentinels that are generated after exposures at mucosal sites. In this experiment, neonatal (day of life 4-6) or adult (6-8 week old) mice were infected with human metapneumovirus (HMPV). 5 weeks following infection, tissue resident cells were identified using i.v. exclusion of circulating cells and flow sorted. Cells were then multiplexed and processed using the 10X genomics platform.
Project description:Internal N6-methyladenosine (m6A) modification of RNA is one of the most common and abundant modifications in eukaryotic cells as well as in viruses. However, the biological role(s) of RNA m6A in virus-host interaction remains elusive. Using human metapneumovirus (hMPV), a medically important non-segmented negative-sense RNA virus as a model, we demonstrate that m6A serves as a molecular marker for innate immune discrimination self and nonself RNAs. We show that hMPV RNAs are m6A methylated and that viral m6A methylation promotes hMPV replication and gene expression. HMPV infection leads to differential expression of interferon-related genes involved in innate immune signaling pathways. Inactivating these m6A sites with synonymous mutations resulted in m6A deficient recombinant hMPVs that induced significantly higher expression of type I interferon that restricted viral replication. Notably, the induction of type I interferons by m6A-deficient rhMPVs and virion RNA was dependent on the cytoplasmic RNA sensor RIG-I, not MDA5. Mechanistically, m6A-deficient virion RNA induces higher expression of RIG-I, enhances its binding affinity to RIG-I, and facilitates the conformational change of RIG-I, leading to enhanced induction of type I IFN expression. The replication of m6A-deficient rhMPVs was attenuated in wild type A459 cells but was restored in cells knocked out for RIG-I and MAVS. Furthermore, m6A-deficient rhMPVs triggered higher type I interferon in vivo and were significantly attenuated in the lower respiratory tract yet retained high immunogenicity in cotton rats. Collectively, our results highlight that (i) virus acquires m6A in their RNAs as a means of mimicking cellular RNA to avoid the detection by innate immunity; and (ii) viral m6A RNA can serve as a novel target to attenuate hMPV for vaccine purposes.
Project description:We infected human lung adenocarcinoma A549 cells with multiple nonsegmented negative-sense (NNS) RNA viruses, including Human metapneumovirus (hMPV), Mumps virus (MuV), Vesicular stomatitis virus (VSV), and Sendai virus (SeV), and evaluated the differences among these viruses in activating innate immune signaling pathways in epithelial cells through transcriptomic analyses of infected cells. Furthermore, by integrating the effects of viral infection on the m6A landscape of A549 cell transcripts, we analyzed the correlation between m6A epitranscriptomic regulation and the activation of innate immunity–related transcripts, as well as the role of m6A in viral immune evasion.
