Epigenetic responses to rhinovirus exposure in airway epithelial cells are correlated with key transcriptional pathways in chronic rhinosinusitis

Background: Viruses may drive immune mechanisms responsible for chronic rhinosinusitis with nasal polyposis (CRSwNP), but little is known about the underlying molecular mechanisms. Objectives: To identify epigenetic and transcriptional responses to a common upper respiratory pathogen, rhinovirus (RV), that are specific to patients with CRSwNP using a primary sinonasal epithelial cell culture model. Methods: Airway epithelial cells were collected at surgery from patients with CRSwNP (cases) and from controls without sinus disease, cultured, and then exposed to RV or vehicle for 48 h. Differential gene expression and DNA methylation (DNAm) between cases and controls in response to RV were determined using linear mixed models. Weighted gene co-expression analysis (WGCNA) was used to identify (a) co-regulated gene expression and DNAm signatures, and (b) genes, pathways, and regulatory mechanisms specific to CRSwNP. Results: We identified 5585 differential transcriptional and 261 DNAm responses (FDR Conclusion: RV activates specific epigenetic programs and correlated transcriptional networks in the sinonasal epithelium of individuals with CRSwNP. These novel observations suggest epigenetic signatures specific to patients with CRSwNP modulate response to viral pathogens at the mucosal environmental interface. Determining how viral response pathways are involved in epithelial inflammation in CRSwNP could lead to therapeutic targets for this burdensome airway disorder.</p

<i>De novo</i> Genome Assembly of the Fungal Plant Pathogen <i>Pyrenophora semeniperda</i>

<div><p><i>Pyrenophora semeniperda</i> (anamorph <i>Drechslera campulata</i>) is a necrotrophic fungal seed pathogen that has a wide host range within the Poaceae. One of its hosts is cheatgrass (<i>Bromus tectorum</i>), a species exotic to the United States that has invaded natural ecosystems of the Intermountain West. As a natural pathogen of cheatgrass, <i>P. semeniperda</i> has potential as a biocontrol agent due to its effectiveness at killing seeds within the seed bank; however, few genetic resources exist for the fungus. Here, the genome of <i>P. semeniperda</i> isolate assembled from sequence reads of 454 pyrosequencing is presented. The total assembly is 32.5 Mb and includes 11,453 gene models encoding putative proteins larger than 24 amino acids. The models represent a variety of putative genes that are involved in pathogenic pathways typically found in necrotrophic fungi. In addition, extensive rearrangements, including inter- and intrachromosomal rearrangements, were found when the <i>P. semeniperda</i> genome was compared to <i>P. tritici-repentis</i>, a related fungal species.</p></div

SyMap dot plot of alignment between <i>P. semeniperda</i> scaffold 1 and <i>P. tritici-repentis</i> 2, 3, 6 and 10.

<p>The <i>P. semeniperda</i> scaffold is displayed along the x-axis and the <i>P. tritici-repentis</i> chromosomes along the y-axis. Boxes highlight regions of homology between the two genomes.</p

SyMap dot plot of <i>P. semeniperda</i> scaffold 6 and <i>P. tritici-repentis</i> chromosome 7.

<p>The dot plot alignment displays <i>P. tritici-repentis</i> chromosome 7 on the x-axis and <i>P. semeniperda</i> scaffold 6 on the y-axis. Boxes highlight regions of homology between the two genome regions.</p

Circular view of the genome alignment between 19 <i>P. semeniperda</i> (Ps) scaffolds and 11 <i>P. tritici-repentis</i> (Ptr) chromosomes.

<p>The numbers marked on each scaffold or chromosome indicate length in megabases.</p

Length distribution of putative genes from <i>P. semeniperda</i>.

<p>Each of the 11,453 gene model is included on the X-axis from smallest to largest (left to right) with its length plotted on the Y-axis.</p

Common GO terms associated with secreted gene products.

<p>Molecular function GO terms are limited to level 3; GO term associated secretion gene products; adapted from Ellwood et al., 2010.</p

SyMap dot plot of genome alignment between <i>P. semeniperda</i> scaffolds and <i>P. tritici-repentis</i> chromosomes.

<p>The <i>P. semeniperda</i> scaffolds are numbered along the x-axis across the top and the <i>P. tritici-repentis</i> chromosomes are numbered on the y-axis along the left of the figure. Boxes highlight regions of homology between the two genomes.</p