IFI27 may predict and evaluate the severity of respiratory syncytial virus infection in preterm infants

Gao, Junyan; Zhu, Xueping; Wu, Mingfu; Jiang, Lijun; Wang, Fudong; He, Shan

doi:10.1186/s41065-020-00167-5

Cited by 18 publications

(9 citation statements)

References 36 publications

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“…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 IFI27 L1 in the blood, rather than IFI27 itself, was associated with disease severity.…”

Section: Discussionsupporting

confidence: 72%

“…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 outcomes 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 (8)(9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2023

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PurposeRobust biomarkers that predict disease outcomes amongst COVID-19 patients are necessary for both patient triage and resource prioritisation. Numerous candidate biomarkers have been proposed for COVID-19. However, at present, there is no consensus on the best diagnostic approach to predict outcomes in infected patients. Moreover, it is not clear whether such tools would apply to other potentially pandemic pathogens and therefore of use as stockpile for future pandemic preparedness.MethodsWe conducted a multi-cohort observational study to investigate the biology and the prognostic role of interferon alpha-inducible protein 27 (IFI27) in COVID-19 patients.ResultsWe show that IFI27 is expressed in the respiratory tract of COVID-19 patients and elevated IFI27 expression in the lower respiratory tract is associated with the presence of a high viral load. We further demonstrate that the systemic host response, as measured by blood IFI27 expression, is associated with COVID-19 infection. For clinical outcome prediction (e.g., respiratory failure), IFI27 expression displays a high sensitivity (0.95) and specificity (0.83), outperforming other known predictors of COVID-19 outcomes. Furthermore, IFI27 is upregulated in the blood of infected patients in response to other respiratory viruses. For example, in the pandemic H1N1/09 influenza virus infection, IFI27-like genes were highly upregulated in the blood samples of severely infected patients.ConclusionThese data suggest that prognostic biomarkers targeting the family of IFI27 genes could potentially supplement conventional diagnostic tools in future virus pandemics, independent of whether such pandemics are caused by a coronavirus, an influenza virus or another as yet-to-be discovered respiratory virus.

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Section: Discussionsupporting

confidence: 72%

Section: Introductionmentioning

confidence: 99%

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

et al. 2023

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“…In proteasomeassociated autoinflammatory cell models, the activation of EIF2AK2 is discovered responding to the decreased proteasome function (40). Numerous studies have demonstrated the indispensable role of IFI27 (Interferon (IFN)-a-inducible protein 27) in SLE (41)(42)(43). IFI27 is strongly correlated with the levels of T helper type 1 (Th1) cells, T helper type 2 (Th2) cells and activated dendritic cells (aDC), and the up-regulation of IFI27 is highly related to many inflammatory events induced by these immune cells (44,45).…”

Section: Discussionmentioning

confidence: 99%

Screening Biomarkers for Systemic Lupus Erythematosus Based on Machine Learning and Exploring Their Expression Correlations With the Ratios of Various Immune Cells

et al. 2022

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BackgroundSystemic lupus erythematosus (SLE) is an autoimmune illness caused by a malfunctioning immunomodulatory system. China has the second highest prevalence of SLE in the world, from 0.03% to 0.07%. SLE is diagnosed using a combination of immunological markers, clinical symptoms, and even invasive biopsy. As a result, genetic diagnostic biomarkers for SLE diagnosis are desperately needed.MethodFrom the Gene Expression Omnibus (GEO) database, we downloaded three array data sets of SLE patients’ and healthy people’s peripheral blood mononuclear cells (PBMC) (GSE65391, GSE121239 and GSE61635) as the discovery metadata (nSLE = 1315, nnormal = 122), and pooled four data sets (GSE4588, GSE50772, GSE99967, and GSE24706) as the validate data set (nSLE = 146, nnormal = 76). We screened the differentially expressed genes (DEGs) between the SLE and control samples, and employed the least absolute shrinkage and selection operator (LASSO) regression, and support vector machine recursive feature elimination (SVM-RFE) analyze to discover possible diagnostic biomarkers. The candidate markers’ diagnostic efficacy was assessed using the receiver operating characteristic (ROC) curve. The reverse transcription quantitative polymerase chain reaction (RT-qPCR) was utilized to confirm the expression of the putative biomarkers using our own Chinese cohort (nSLE = 13, nnormal = 10). Finally, the proportion of 22 immune cells in SLE patients was determined using the CIBERSORT algorithm, and the correlations between the biomarkers’ expression and immune cell ratios were also investigated.ResultsWe obtained a total of 284 DEGs and uncovered that they were largely involved in several immune relevant pathways, such as type І interferon signaling pathway, defense response to virus, and inflammatory response. Following that, six candidate diagnostic biomarkers for SLE were selected, namely ABCB1, EIF2AK2, HERC6, ID3, IFI27, and PLSCR1, whose expression levels were validated by the discovery and validation cohort data sets. As a signature, the area under curve (AUC) values of these six genes reached to 0.96 and 0.913, respectively, in the discovery and validation data sets. After that, we checked to see if the expression of ABCB1, IFI27, and PLSCR1 in our own Chinese cohort matched that of the discovery and validation sets. Subsequently, we revealed the potentially disturbed immune cell types in SLE patients using the CIBERSORT analysis, and uncovered the most relevant immune cells with the expression of ABCB1, IFI27, and PLSCR1.ConclusionOur study identified ABCB1, IFI27, and PLSCR1 as potential diagnostic genes for Chinese SLE patients, and uncovered their most relevant immune cells. The findings in this paper provide possible biomarkers for diagnosing Chinese SLE patients.

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“…Viperin is also the most upregulated gene in human nasal epithelium following intranasal challenge with Rhinovirus 49 . Another RSV-related gene is I27L2 , the top upregulated gene in S. hispidus and S. fulviventer that is also the top differentially expressed gene in preterm infants with severe RSV infection 50 . Other upregulated genes also shown to be involved in RSV infection include chemokines CXCL10 51 , CXCL11 52 , LY6E 53 , MX2 54 , OAS1A 55 , ISG15 56 , IRF9 57 , NLRC5 58 and K2C6A 59 .…”

Section: Discussionmentioning

confidence: 99%

Species-specific transcriptomic changes upon respiratory syncytial virus infection in cotton rats

Strickland

Rajagopala

Kamali

et al. 2022

Sci Rep

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The cotton rat (Sigmodon) is the gold standard pre-clinical small animal model for respiratory viral pathogens, especially for respiratory syncytial virus (RSV). However, without a reference genome or a published transcriptome, studies requiring gene expression analysis in cotton rats are severely limited. The aims of this study were to generate a comprehensive transcriptome from multiple tissues of two species of cotton rats that are commonly used as animal models (Sigmodon fulviventer and Sigmodon hispidus), and to compare and contrast gene expression changes and immune responses to RSV infection between the two species. Transcriptomes were assembled from lung, spleen, kidney, heart, and intestines for each species with a contig N50 > 1600. Annotation of contigs generated nearly 120,000 gene annotations for each species. The transcriptomes of S. fulviventer and S. hispidus were then used to assess immune response to RSV infection. We identified 238 unique genes that are significantly differentially expressed, including several genes implicated in RSV infection (e.g., Mx2, I27L2, LY6E, Viperin, Keratin 6A, ISG15, CXCL10, CXCL11, IRF9) as well as novel genes that have not previously described in RSV research (LG3BP, SYWC, ABEC1, IIGP1, CREB1). This study presents two comprehensive transcriptome references as resources for future gene expression analysis studies in the cotton rat model, as well as provides gene sequences for mechanistic characterization of molecular pathways. Overall, our results provide generalizable insights into the effect of host genetics on host-virus interactions, as well as identify new host therapeutic targets for RSV treatment and prevention.

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IFI27 may predict and evaluate the severity of respiratory syncytial virus infection in preterm infants

Cited by 18 publications

References 36 publications

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

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

Screening Biomarkers for Systemic Lupus Erythematosus Based on Machine Learning and Exploring Their Expression Correlations With the Ratios of Various Immune Cells

Species-specific transcriptomic changes upon respiratory syncytial virus infection in cotton rats

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