Innovative biomarkers TCN2 and LY6E can significantly inhibit respiratory syncytial virus infection.

Cao B ，Li M ，Li X ，Ji X ，Wan L ，Jiang Y ，Zhou L ，Gong F ，Chen X ... -  《Journal of Translational Medicine》

Identification of potential immune/diagnosis related gene-immunocyte subtype networks in extracellular immune response to respiratory syncytial virus infection.

Respiratory syncytial virus (RSV) is one of the important pathogenic agents of pediatric respiratory tract infection. Weighted gene co-expression network analysis (WGCNA) is used to study autoimmune diseases, which can find potential hub genes. The diagnostic model based on hub genes and machine learning makes it possible to diagnose the extracellular immune response to RSV infection early. The aim of the present study was to identify potential immune, diagnose and treatment related genes expressed in RSV-infected cells. Firstly, gene expression data were downloaded from the Gene Expression Omnibus (GEO) to identify differentially expressed genes (DEGs). Secondly, WGCNA was performed based on DEGs to obtain hub genes related to immunity score. Thirdly, protein-protein interaction (PPI) and the immune infiltration analysis of hub immune related genes were performed. Finally, diagnostic and immune related genes were identified by machine learning, followed by functional analysis. Totally, 2063 DEGs were identified in the extracellular immune response to RSV infection. Among which, 10 key immune and diagnosis related genes were identified, including ITGA2B, GP9, ITGB3, SELP, PPBP, MPL, CXCL8, NFE2, PTGS1 and LY6G6F. Several immune/diagnosis related gene-immunocyte subtype networks were identified, such as CXCL8-Type 17 T helper cell, LY6G6F-CD56 bright natural killer cell, PPBP-activated CD4 T cell/T follicular helper cell, NFE2/PTGS1/SELP-activated dendritic cell, GP9/ITGA2B/MPL-activated CD8 T cell. ITGB3, MPL and PTGS1 could be considered as therapeutic targets. Some significantly enriched signaling pathways were identified, including hematopoietic cell lineage (involving GP9 and ITGA2B), cytokine-cytokine receptor interaction (involving MPL), chemokine signaling pathway (involving PPBP) and arachidonic acid metabolism (involving PTGS1). The 10-immune related gene signature may be used as potential diagnostic markers for the extracellular immune response to RSV infection, which may provide a new field in searching for diagnostic and therapeutic molecules in the extracellular immune response to RSV infection.

Wang B ，Liu H 《-》

A novel combined nomogram for predicting severe acute lower respiratory tract infection in children hospitalized for RSV infection during the post-COVID-19 period.

Liu HF ，Zhang XZ ，Liu CY ，Li W ，Li WH ，Wang YY ，Li HY ，Xiang M ，Lu R ，Yuan TY ，Fu HM ... -  《Frontiers in Immunology》

Long Noncoding RNA NRAV Promotes Respiratory Syncytial Virus Replication by Targeting the MicroRNA miR-509-3p/Rab5c Axis To Regulate Vesicle Transportation.

Respiratory syncytial virus (RSV) is an enveloped RNA virus which is responsible for approximately 80% of lower respiratory tract infections in children. Current lines of evidence have supported the functional involvement of long noncoding RNA (lncRNA) in many viral infectious diseases. However, the overall biological effect and clinical role of lncRNAs in RSV infection remain unclear. In this study, lncRNAs related to respiratory virus infection were obtained from the lncRNA database, and we collected 144 clinical sputum specimens to identify lncRNAs related to RSV infection. Quantitative PCR (qPCR) detection indicated that the expression of lncRNA negative regulator of antiviral response (NRAV) in RSV-positive patients was significantly lower than that in uninfected patients, but lncRNA psoriasis-associated non-protein coding RNA induced by stress (PRINS), nuclear paraspeckle assembly transcript 1 (NEAT1), and Nettoie Salmonella pas Theiler's (NeST) showed no difference in vivo and in vitro Meanwhile, overexpression of NRAV promoted RSV proliferation in A549 and BEAS-2B cells, and vice versa, indicating that the downregulation of NRAV was part of the host antiviral defense. RNA fluorescent in situ hybridization (FISH) confirmed that NRAV was mainly located in the cytoplasm. Through RNA sequencing, we found that Rab5c, which is a vesicle transporting protein, showed the same change trend as NRAV. Subsequent investigation revealed that NRAV was able to favor RSV production indirectly by sponging microRNA miR-509-3p so as to release Rab5c and facilitate vesicle transportation. The study provides a new insight into virus-host interaction through noncoding RNA, which may contribute to exploring potential antivirus targets for respiratory virus.IMPORTANCE The mechanism of interaction between RSV and host noncoding RNAs is not fully understood. In this study, we found that the expression of long noncoding RNA (lncRNA) negative regulator of antiviral response (NRAV) was reduced in RSV-infected patients, and overexpression of NRAV facilitated RSV production in vitro, suggesting that the reduction of NRAV in RSV infection was part of the host antiviral response. We also found that NRAV competed with vesicle protein Rab5c for microRNA miR509-3p in cytoplasm to promote RSV vesicle transport and accelerate RSV proliferation, thereby improving our understanding of the pathogenic mechanism of RSV infection.

Li J ，Li M ，Wang X ，Sun M ，Ma C ，Liang W ，Gao X ，Wei L ... -  《-》

Andrographolide Attenuates RSV-induced Inflammation by Suppressing Apoptosis and Promoting Pyroptosis after Respiratory Syncytial Virus Infection In Vitro.

Respiratory syncytial virus (RSV), which is the predominant viral pathogen responsible for causing acute lower respiratory tract infections in children, currently lacks specific therapeutic drugs. Despite andrographolide's demonstrated effectiveness against various viral infections, its effects on RSV infection remain unclear. In this study, RSV infection and andrographolide-intervened A549 cell lines were used. The virus load of RSV and the levels of IL-6 and IL-8 in the cell supernatant were quantified. The potential targets of andrographolide in the treatment of RSV-infected airway epithelial cells were analyzed using the Gene Expression Omnibus (GEO) database and the PharmMapper Database, and the changes in mRNA expression of these target genes were measured. To further illustrate the effect of andrographolide on the death pattern of RSV-infected airway epithelial cells, Annexin V-FITC/PI apoptosis assays and Western blotting were conducted. Andrographolide decreased the viral load and attenuated IL-6 and IL-8 levels in cell supernatant post-RSV infection. A total of 25 potential targets of andrographolide in the treatment of RSV-infected airway epithelial cells were discovered, and CASP1, CCL5, JAK2, and STAT1 were identified as significant players. Andrographolide noticeably suppressed the increased mRNA expressions of these genes post-RSV infection as well as IL-1β. The flow cytometry analysis demonstrated that andrographolide alleviated apoptosis in RSV-infected cells. Additionally, RSV infection decreased the protein levels of caspase-1, cleaved caspase-1, cleaved IL-1β, N-terminal of GSDMD, and Bcl-2. Conversely, andrographolide increased their levels. These results suggest that andrographolide may reduce RSV-induced inflammation by suppressing apoptosis and promoting pyroptosis in epithelial cells, leading to effective viral clearance.

Che S ，Xie X ，Lin J ，Liu Y ，Xie J ，Liu E ... -  《-》