IFITM1 suppresses expression of human endogenous retroviruses in human embryonic stem cells

Fu, Yudong; Zhou, Zhongli; Wang, Hua; Gong, Peng; Guo, Renpeng; Wang, Jinmiao; Lu, Xinyi; Qi, Feng; Liu, Lin

doi:10.1002/2211-5463.12246

Cited by 12 publications

(11 citation statements)

References 39 publications

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“…Interferon induced transmembrane protein 1 (IFITM1) is a member of interferon-induced transmembrane proteins and can be activated by various viruses. IFITM1 inhibits the entry of viruses to the host cell cytoplasm, permits endocytosis and prevents subsequent viral fusion and release of viral contents into the cytosol [ 32 – 34 ]. Interferon induced protein 44 (IFI44) and interferon induced protein 44 like (IFI44L), an important paralog of IFI44, are associated with the formation of microtubular structures as well as exhibiting a low antiviral activity against hepatitis C virus [ 33 , 35 , 36 ].…”

Section: Discussionmentioning

confidence: 99%

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

Gao

Zhu

et al. 2021

Hereditas

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Background Preterm infants are a special population that vulnerable to respiratory syncytial virus (RSV) infection and the lower respiratory tract infections (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.

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Section: Discussionmentioning

confidence: 99%

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

Gao

Zhu

et al. 2021

Hereditas

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“…Among human pathogens, RV is rather exceptional in its ability to replicate noncytopathically in iPSCs, which in general represent a rather restrictive environment to most viral infections [43]. The protection of human development from a pathogenic insult involves several mechanisms, including transcriptional silencing of viruses in pluripotent stem cells [44] and an intrinsic high expression level of IFN-induced genes [14].…”

Section: Discussionmentioning

confidence: 99%

“…The protection of human development from a pathogenic insult involves several mechanisms, including transcriptional silencing of viruses in pluripotent stem cells [44] and an intrinsic high expression level of IFN-induced genes [14]. This includes interferon-induced transmembrane protein 1 (IFITM1) and its capacity to restrict the potentially harmful reactivation of human endogenous retroviruses [43]. Otherwise, the antiviral innate immune response in iPSCs is rather refractive [15].…”

Section: Discussionmentioning

confidence: 99%

Teratogenic Rubella Virus Alters the Endodermal Differentiation Capacity of Human Induced Pluripotent Stem Cells

Bilz

Willscher

Binder

et al. 2019

Cells

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The study of congenital virus infections in humans requires suitable ex vivo platforms for the species-specific events during embryonal development. A prominent example for these infections is rubella virus (RV) which most commonly leads to defects in ear, heart, and eye development. We applied teratogenic RV to human induced pluripotent stem cells (iPSCs) followed by differentiation into cells of the three embryonic lineages (ecto-, meso-, and endoderm) as a cell culture model for blastocyst- and gastrulation-like stages. In the presence of RV, lineage-specific differentiation markers were expressed, indicating that lineage identity was maintained. However, portrait analysis of the transcriptomic expression signatures of all samples revealed that mock- and RV-infected endodermal cells were less related to each other than their ecto- and mesodermal counterparts. Markers for definitive endoderm were increased during RV infection. Profound alterations of the epigenetic landscape including the expression level of components of the chromatin remodeling complexes and an induction of type III interferons were found, especially after endodermal differentiation of RV-infected iPSCs. Moreover, the eye field transcription factors RAX and SIX3 and components of the gene set vasculogenesis were identified as dysregulated transcripts. Although iPSC morphology was maintained, the formation of embryoid bodies as three-dimensional cell aggregates and as such cellular adhesion capacity was impaired during RV infection. The correlation of the molecular alterations induced by RV during differentiation of iPSCs with the clinical signs of congenital rubella syndrome suggests mechanisms of viral impairment of human development.

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“…Emerging research suggests that IFN signaling plays an important role in the tumor microenvironment and affects anti-cancer therapies differentially (Diamond and Farzan, 2013; Liu et al, 2018; Patin et al, 2018). IFITM1 is a member of the IFN-stimulated gene (ISG) family and an essential mediator of interferon-alpha, -beta and -gamma-mediated inhibition of cell proliferation and cell adhesion signaling (Johnson et al, 2006; Fu et al, 2017). It is largely known for the importance in many cellular functions, such as proliferation and adhesion.…”

Section: Discussionmentioning

confidence: 99%

The Therapeutic Potential of Adipose Tissue-Derived Mesenchymal Stem Cells to Enhance Radiotherapy Effects on Hepatocellular Carcinoma

Tang

Yin

et al. 2019

Front. Cell Dev. Biol.

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Several studies have investigated strategies to improve the clinical efficacy of radiotherapy (RT) against hepatocellular carcinoma (HCC), yet the prognosis remains poor. Human adipose tissue-derived mesenchymal stem cells (AT-MSCs), easily accessible and abundant in quantity, have represented as an attractive therapeutic tool for the stem cell-based treatment for cancer diseases. Through direct co-culture and indirect separate culture experiments, we showed that AT-MSCs could enhance inhibitory effect of RT on reducing HCC cell growth, migration and invasion in both in vitro and in vivo experiments. RNA-sequencing analysis revealed a noticeable interferon-induced transmembrane 1 (IFITM1)-induced tumor gene signature. Gain and loss of mechanistic studies indicated that mechanism was attributed to downregulated expression of signal transducer and activator of transcription 3 (STAT3) and matrix metallopeptidases (MMPs) and upregulated expression of P53 and caspases. Collectively, our findings suggest that AT-MSCs might enhance the therapeutic effects of RT on HCC, providing a rationale for AT-MSCs and RT combination therapy as a new remedy for HCC.

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IFITM1 suppresses expression of human endogenous retroviruses in human embryonic stem cells

Cited by 12 publications

References 39 publications

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

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

Teratogenic Rubella Virus Alters the Endodermal Differentiation Capacity of Human Induced Pluripotent Stem Cells

The Therapeutic Potential of Adipose Tissue-Derived Mesenchymal Stem Cells to Enhance Radiotherapy Effects on Hepatocellular Carcinoma

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