IFI27 May Predict and Evaluate the Severity of Respiratory Syncytial Virus Infection in Preterm Infants

Abstract

Background: Preterm infants are a special population that vulnerable to respiratory syncytial virus (RSV) infection and the lower respiratory tract infection (LRTIs) caused by RSV could be severe and even life-threating. The purpose of the present study was to identify candidate genes of preterm infants who are susceptible to RSV infection and provide a new insight into the pathogenesis of RSV infection. Methods: Three datasets (GSE77087, GSE69606 and GSE41374) containing 183 blood samples of RSV infected patients and 33 blood samples of healthy controls from Gene Expression Omnibus (GEO) database were downloaded and the differentially expressed genes (DEGs) were screened out. The function and pathway enrichments were analyzed through Database for Annotation, Visualization and Integrated Discovery (DAVID) website. The protein‐protein interaction (PPI) network for DEGs was constructed through Search Tool for the Retrieval of Interacting Genes (STRING). The module analysis was performed by Cytoscape software and hub genes were identified. Clinical verification was employed to verify the expression level of top five hub genes among 72 infants including 50 RSV infected patients and 22 non-RSV-infected patients hospitalized in our center. Further, the RSV infected infants with high-expression IFI27 and those with low-expression IFI27 were compared (defined as higher or lower than the median mRNA level). Finally, the gene set enrichment analysis (GSEA) focusing on IFI27 was carried out. Results: Totally, 4028 DEGs were screened out and among which, 131 most significant DEGs were selected. Subsequently, 13 hub genes were identified and function and pathway enrichments of hub genes mainly were: response to virus, defense response to virus, regulation of viral genome replication and regulation of viral life cycle. Furthermore, IFI27 was confirmed to be the most significantly expressed in clinical verification. Gene sets associated with calcium signaling pathway, arachidonic acid metabolism, extracellular matrix receptor interaction and so on were significantly enriched when IFI27 was highly expressed. Moreover, high-expression IFI27 was associated with more severe cases (p=0.041), more requirements of mechanical ventilation (p=0.034), more frequent hospitalization (p<0.001) and longer cumulative hospital stay (p=0.012). Conclusion: IFI27 might serve to predict RSV infection and evaluate the severity of RSV infection in preterm infants.

IFI27 transcription is an early predictor for COVID-19 outcomes; a multi-cohort observational study

“…As a component of the anti-viral interferon response, it is not surprising that elevated IFI27 expression was observed in the blood of patients infected with a broad range of different respiratory viruses but not in the blood of patients with a bacterial respiratory infection. These data, combined with previous suggestions that IFI27 expression is associated with the severity of RSV [6, 7], suggest that IFI27 may represent a pan-viral prognostic biomarker. Interestingly, when we investigated this further in the context of influenza virus, we found that expression of IFI27L1 in the blood, rather than IFI27 itself, was associated with disease severity.…”

“…IFI27 (also known as ISG12 or p27) is an interferon alpha (and to a lesser extent interferon gamma) inducible gene of unknown function, with the gene product residing in the nuclear membrane of the cell [5]. IFI27 expression is associated with the severity of several different viral illnesses including respiratory syncytial virus (RSV) infection and Enterovirus 71 (EV71) hand foot and mouth disease [6,7]. Preliminary evidence suggests that IFI27 expression may be a useful biomarker for COVID-19 diagnosis and severity [8][9][10][11].…”

Filaggrin and cytokines in respiratory samples of preterm infants at risk for respiratory viral infection

“…Adaptative immune responses may influence the risk of viral infections in newborns as their CD4 + T cells have delayed synthesis of IFNγ and IL-2 in presence of viral infections 40,43 . Genetic studies can be very helpful in the determination of risk factors, such as mannose-binding lectin (MBL) mutations causing MBL deficiency, which are associated with higher risk of sepsis in preterm neonates 44 , or increased IFI27 expression, associated with higher RSV infection severity 45 .…”

Blood-based Genomic and Cellular Determinants of Response to Neoadjuvant PD-1 Blockade in Patients with Non-Small-Cell Lung Cancer

“…These findings were significant as they were, on one hand, validated by multiple approaches (RNA-seq, qRT-PCR and GENT2 microarray database); on the other hand, they were also confirmed by multiple datasets and diverse cohorts (LCE meta-analysis database). This gene signature group contains a modulator of innate immune responses (IFN-I signal-induced gene IFI27) [34, 35], a hematopoietic transcription regulator (GATA2) [36], a metabolism mediator (ANKRD22) [37, 38], and a transcription factor involved in differentiation control (LHX4) [39], which is consistent with the following findings that immunological and metabolism mechanisms are enriched in post-treatment and responder patients ( Figure 6 A & 6B ). Moreover, several of them were proven to regulate the oncogenesis of lung cancer or respiratory diseases.…”