The Immunomodulatory CEA Cell Adhesion Molecule 6 (CEACAM6/CD66c) Is a Protein Receptor for the Influenza A Virus

Rahman, Shah Kamranur; Ansari, Mairaj Ahmed; Gaur, Pratibha; Ahmad, Imtiyaz; Chakravarty, Chandrani; Verma, Deepali; Sharma, Anshika; Chhibber, Sanjay; Nehal, Naila; Wirth, Dagmar; Lal, Sunil K.

doi:10.3390/v13050726

Cited by 14 publications

(17 citation statements)

References 44 publications

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“…The treatment of anti-sialylated glycoprotein CD83 on dendritic cells and macrophages could reduce influenza A virus-lung injury and in mice [ 37 ]. Influenza A virus can also use a host adhesion molecule on surface CD66c as a novel receptor that binds to viral NA during entry into A549 and HEK293 cells [ 38 ]. Since both of them have immune functions and present on primary human T cells, the exploration of their roles in early infection with the influenza A virus should be taken seriously for some time to come.…”

Section: Discussionmentioning

confidence: 99%

Pandemic influenza A (H1N1) virus causes abortive infection of primary human T cells

Jia

et al. 2022

Emerging Microbes & Infections

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Influenza A virus still represents a noticeable epidemic risk to international public health at present, despite the extensive use of vaccines and anti-viral drugs. In the fight against pathogens, the immune defence lines consisting of diverse lymphocytes are indispensable for humans. However, the role of virus infection of lymphocytes and subsequent abnormal immune cell death remains to be explored. Different T cell subpopulations have distinct characterizations and functions, and we reveal the high heterogeneity of susceptibility to viral infection and biological responses such as apoptosis in various CD4 + T and CD8 + T cell subsets through single-cell transcriptome analyses. Effector memory CD8 + T cells (CD8 + T EM ) that mediate protective memory are identified as the most susceptible subset to pandemic influenza A virus infection among primary human T cells. Non-productive infection is established in CD8 + T EM and naïve CD8 + T cells, which indicate the mechanism of intracellular antiviral activities for inhibition of virus replication such as abnormal viral splicing efficiency, incomplete life cycles and up-regulation of interferon-stimulated genes in human T cells. These findings provide insights into understanding lymphopenia and the infectious mechanisms of pandemic influenza A virus and broad immune host–pathogen interactional atlas in primary human T cells.

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Section: Discussionmentioning

confidence: 99%

Pandemic influenza A (H1N1) virus causes abortive infection of primary human T cells

Jia

et al. 2022

Emerging Microbes & Infections

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“…For example, a recent study has shown that IAV does not directly bind to EGFR, but the binding of IAV with multivalent sialic acid clusters can trigger EGFR activation ( 56 ). However, the glycoprotein carcinoembryonic antigen-related cell adhesion molecule 6 (CD66c or CEACAM6) has recently been identified as a receptor for IAV infection ( 57 ), and further research will undoubtedly identify more such interacting receptors in the future. After binding to cellular receptors, IAV is taken up by cells via either clathrin- or caveolin-dependent endocytosis, which usually occurs at lipid rafts ( Figure 1 ) ( 50 , 58 ).…”

Section: Iav Internalization Relies On Lipid Raftsmentioning

confidence: 99%

Modulating cholesterol-rich lipid rafts to disrupt influenza A virus infection

Chen

Yang

et al. 2022

Front. Immunol.

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Influenza A virus (IAV) is widely disseminated across different species and can cause recurrent epidemics and severe pandemics in humans. During infection, IAV attaches to receptors that are predominantly located in cell membrane regions known as lipid rafts, which are highly enriched in cholesterol and sphingolipids. Following IAV entry into the host cell, uncoating, transcription, and replication of the viral genome occur, after which newly synthesized viral proteins and genomes are delivered to lipid rafts for assembly prior to viral budding from the cell. Moreover, during budding, IAV acquires an envelope with embedded cholesterol from the host cell membrane, and it is known that decreased cholesterol levels on IAV virions reduce infectivity. Statins are commonly used to inhibit cholesterol synthesis for preventing cardiovascular diseases, and several studies have investigated whether such inhibition can block IAV infection and propagation, as well as modulate the host immune response to IAV. Taken together, current research suggests that there may be a role for statins in countering IAV infections and modulating the host immune response to prevent or mitigate cytokine storms, and further investigation into this is warranted.

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“…Thus, M59 was associated with severe in uenza development. M59 hub gene CEACAM6 has been reported as a protein receptor for the in uenza A virus [24].…”

Section: Module Expression Was Changed In Severe a (H1n1) Pandemic In...mentioning

confidence: 99%

Construction of gene network database, and identification of key genes for diagnosis, prognosis, and treatment in sepsis

Li¹,

Qu²,

Miao³

et al. 2022

Preprint

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Sepsis and sepsis-related diseases cause a high rate of mortality worldwide. The molecular and cellular mechanisms of sepsis are still unclear. Six sepsis-related blood transcriptome datasets were collected and analyzed by weighted gene co-expression network analysis (WGCNA). Functional annotation was performed in gProfiler tool. DSigDB was used for drug signatures enrichment analysis. The proportion of immune cells was estimated by the CIBERSORT tool. The relationships between modules, immune cells, and survival were identified by correlation analysis and survival analysis. A total of 37 stable co-expressed gene modules were identified. These modules were associated with the critical biology process in sepsis. Four modules can independently separate patients with long and short survival. Three modules can recurrently separate sepsis and normal patients with high accuracy. Some modules can separate bacterial pneumonia, influenza pneumonia, mixed bacterial and influenza A pneumonia, and non-infective systemic inflammatory response syndrome (SIRS). Drug signature analysis identified drugs associated with sepsis, such as testosterone, phytoestrogens, ibuprofen, urea, dichlorvos, potassium persulfate, and vitamin B12. Finally a gene co-expression network database was constructed (https://liqs.shinyapps.io/sepsis/). In conclusion, the recurrent modules in sepsis may facilitate disease diagnosis, prognosis, and treatment.

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The Immunomodulatory CEA Cell Adhesion Molecule 6 (CEACAM6/CD66c) Is a Protein Receptor for the Influenza A Virus

Cited by 14 publications

References 44 publications

Pandemic influenza A (H1N1) virus causes abortive infection of primary human T cells

Pandemic influenza A (H1N1) virus causes abortive infection of primary human T cells

Modulating cholesterol-rich lipid rafts to disrupt influenza A virus infection

Construction of gene network database, and identification of key genes for diagnosis, prognosis, and treatment in sepsis

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