Findings provide valuable insights into the molecular mechanisms underlying PRRSV infection and pave the way for developing more effective preventive and treatment measures.
Abstract
The porcine reproductive and respiratory syndrome virus (PRRSV) is a highly contagious pathogen. Viral infections often enhance their replication by modulating the structure and expression of host genes. However, it remains unclear whether PRRSV employs a similar mechanism to achieve self-replication. To address this question, the current study combined assay for transposase accessible chromatin sequencing (ATAC-seq) and ribonucleic acid (RNA) sequencing (RNA-seq) to identify accessible chromatin regions and key host genes associated with PRRSV infection. By comparing the PRRSV-infected group with the control group, we initially detected 8664 differentially accessible chromatin regions and 4037 differentially expressed genes. Motif analysis of these differential chromatin regions revealed several potential cis-regulatory elements containing binding sites for transcription factors. Further integration of ATAC-seq and RNA-seq results identified 1352 overlapping genes between the PRRSV-infected and control groups. A significant positive correlation between differential gene expression and chromatin accessibility signals suggests that chromatin remodeling may drive transcriptional changes during infection. Protein–protein interaction (PPI) network analysis highlighted candidate genes potentially associated with PRRSV infection in hosts, such as IL1B, CCL20, CXCL10, CSF3, etc. Given their potential association with the infection mechanism, these genes could serve as candidate targets for the future development of prophylactic vaccines and therapeutic strategies. Additionally, several signaling pathways that may regulate immune and inflammatory responses were significantly enriched in our ATAC-seq and RNA-seq analyses. These findings provide valuable insights into the molecular mechanisms underlying PRRSV infection and pave the way for developing more effective preventive and treatment measures.
Pseudorabies virus (PRV) is an important α-herpesvirus. However, the chromatin state and transcriptional regulatory mechanisms of its genome upon entry into host cell nuclei remain poorly understood. In this study, we employed the Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) and RNA sequencing (RNA-seq) to analyze chromatin accessibility and the transcriptome of the PRV genome in PK15 cells at multiple time points post-infection. ATAC-seq analysis revealed that the proportion of viral reads increased progressively over time, from 0.01% at 4 h to approximately 1.09% and 13% at 8 h and 12 h, respectively. A total of 112 ATAC peaks were identified, distributed across the PRV genome without apparent low-accessibility regions. Fragment length analysis demonstrated that the PRV genome does not adopt the regularly phased nucleosome organization typical of the host genome. RNA-seq analysis detected 66 expressed PRV genes, which were classified into four kinetic expression clusters, corresponding to immediate-early/early (IE/E), early (E), early-to-late transitional (E-L), and late (L) gene groups. Virus–host correlation analysis revealed significant associations between PRV gene expression and multiple host inflammation-related genes. Integrated multi-omics analysis further confirmed the concordance between chromatin accessibility dynamics and transcriptional activity changes. Collectively, these findings indicate that the PRV genome maintains a predominantly open and accessible chromatin state throughout lytic infection, providing new insights into the epigenetic regulatory mechanisms of α-herpesviruses.
Songbai Yang, Kun Teng, Gui-Jun Liu et al.· International Journal of Mol...· 0 citations
Fiber-seq simultaneously profiles chromatin accessibility, DNA methylation, protein footprints, and genetic variation on single molecules at near—base-pair resolution, revealing how genetic and epigenetic features interact to regulate gene expression and provides a powerful new framework for dissecting immune cell function and disease mechanisms.
Emily A Madden, James T. Anderson, M. Cowles et al.· Journal of Immunology· 0 citations
Translation of key viral replicative proteins in coronaviruses requires a programmed –1 ribosomal frameshifting (–1 PRF) event controlled by the viral frameshift-stimulatory element (FSE). Although previous studies have analyzed host factor dependencies of coronaviruses, how host cellular factors alter –1 PRF efficiency and affect viral replication remains poorly understood. Here, using RNA pull-down combined with LC-MS/MS analysis, we identified heterogeneous nuclear ribonucleoprotein C (hnRNPC) as a major interacting protein of FSE RNA. Coronavirus infection triggers hnRNPC mRNA decay, alters hnRNPC protein levels, and induces its cytoplasmic relocalization, where it appears to bind directly to FSE RNA through residues Asn7 and Asn83. This binding is associated with increased –1 PRF efficiency and may facilitate coronavirus replication. Deletion mapping analysis shows that hnRNPC preferentially binds U-rich regions of the FSE RNA. Finally, we demonstrated that the small molecule Elbasvir directly binds hnRNPC, disrupting the interaction between hnRNPC and FSE RNA and inhibiting coronavirus replication by decreasing –1 PRF efficiency. Collectively, our study identifies hnRNPC as a key host cofactor for coronaviruses and provides a novel target for broad-spectrum antiviral drug development.
Jingchen Xu, Hongying Li, Jianrui Li et al.· PLoS Pathogens· 0 citations
Findings suggest that NEAT1 and SNHG17, which have been reported to regulate inflammatory responses in multiple pathological conditions, may play important roles in the host response to L. donovani infection and could serve as potential targets for the prevention and treatment of leishmaniasis.