Topology, Antiviral Functional Residues and Mechanism of IFITM1

Sun, Fang; Xia, Zhiqiang; Han, Yuewen; Gao, Minjun; Wang, Luyao; Wu, Yingliang; Sabatier, Jean‐Marc; Miao, Lei; Cao, Zhijian

doi:10.3390/v12030295

Cited by 17 publications

(15 citation statements)

References 37 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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“…Finally, the sequence analyses and the available literature data prompted to work on the hypothesis of type III TM topology for IFITM2 and IFITM3 proteins. Type III TM topology is characterized by the cell surface exposure of both N- and C-termini (NTD and CTD), respectively linked to two antiparallel transmembrane domains (TM1 and TM2) connected to a short cytosolic inner loop (CIL) (Sun et al, 2020; Weston et al, 2014). Due to their intracellular and intramembrane localization, or their very short length, CIL, TMs and CTD (128-132 aa) were not considered in the selection of the immunogen.…”

Section: Resultsmentioning

confidence: 99%

A specific anti-IFITM2 antibody bars the way to SARS-CoV-2 entry into host cells

Basile

Zannella

Marco

et al. 2022

Preprint

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The early steps of viral infection involve protein complexes and structural lipid rearrangements, which mark the characteristic strategies of each virus in entering permissive host cells. Human IFITM proteins have been described as inhibitors of a broad range of viruses. Despite their homology and functional redundancy, recently it has been surprisingly shown that SARS-CoV-2 is able to specifically hijack the IFITM2 protein. Here has been reported the characterization of a newly generated specific anti-IFITM2 mAb able to impair SARS-CoV-2 Spike protein internalization and, consequently, to reduce the SARS-CoV-2 cytopathic effects and syncytia formation. Importantly, as evidence of the more general involvement of IFITM2 in virus entry, the anti-IFITM2 mAb was able to efficiently reduce HSVs- and RSV- dependent cytopathic effects. Hence, IFITM proteins could be promising targets that can foster the development of biological antiviral molecules, or suggest additional therapeutic strategies for the treatment of viral infections.

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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)(33)(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. 2020

Preprint

View full text Add to dashboard Cite

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.

show abstract

Topology, Antiviral Functional Residues and Mechanism of IFITM1

Cited by 17 publications

References 37 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

A specific anti-IFITM2 antibody bars the way to SARS-CoV-2 entry into host cells

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

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