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LY6E blocks coronavirus fusion and confers immune control of viral disease

ABSTRACT: LY6E blocks coronavirus fusion and confers immune control of viral disease

PROVIDER: PRJNA609134 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11195500_1.fastq.gz	Fastqsanger.gz
	SRR11195500_2.fastq.gz	Fastqsanger.gz
	SRR11195501_1.fastq.gz	Fastqsanger.gz
	SRR11195501_2.fastq.gz	Fastqsanger.gz
	SRR11195502_1.fastq.gz	Fastqsanger.gz

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LY6E blocks coronavirus fusion and confers immune control of viral disease

Project description:Zoonotic coronaviruses (CoVs) are significant threats to global health, as exemplified by the recent emergence of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Host immune responses to CoV are complex and regulated in part through antiviral interferons. However, the interferon-stimulated gene products that inhibit CoV are not well characterized. Here, we show that interferon-inducible lymphocyte antigen 6 complex, locus E (LY6E) potently restricts cellular infection by multiple CoVs, including SARS-CoV, SARS-CoV-2, and Middle East respiratory syndrome coronavirus (MERS-CoV). Mechanistic studies revealed that LY6E inhibits CoV entry into cells by interfering with spike protein-mediated membrane fusion. Importantly, mice lacking Ly6e in hematopoietic cells were highly susceptible to murine CoV infection. Exacerbated viral pathogenesis in Ly6e knockout mice was accompanied by loss of hepatic and splenic immune cells and reduction in global antiviral gene pathways. Accordingly, we found that Ly6e directly protects primary B cells and dendritic cells from murine CoV infection. Our results demonstrate that LY6E is a critical antiviral immune effector that controls CoV infection and pathogenesis. These findings advance our understanding of immune-mediated control of CoV in vitro and in vivo, knowledge that could help inform strategies to combat infection by emerging CoV.

2020-02-28 | GSE146074 | GEO

LY6E is a pan-coronavirus restriction factor in the respiratory tract

Project description:LY6E is an antiviral restriction factor that inhibits coronavirus spike-mediated fusion, but the cell types in vivo that require LY6E for protection from respiratory coronavirus infection are unknown. Here, we used a panel of seven conditional Ly6e knockout mice to define which Ly6e-expressing cells confer control of airway infection by murine coronavirus and SARS-CoV-2. Loss of Ly6e in Lyz2-expressing cells, radioresistant Vav1-expressing cells, and non-hematopoietic cells increased susceptibility to murine coronavirus. Global conditional loss of Ly6e expression resulted in clinical disease and higher viral burden after SARS-CoV-2 infection, but little evidence of immunopathology. We show that Ly6e expression protected secretory club and ciliated cells from SARS-CoV-2 infection and prevented virus-induced loss of an epithelial cell transcriptomic signature in the lung. Our study demonstrates that lineage confined rather than broad expression of Ly6e sufficiently confers resistance to disease caused by murine and human coronaviruses.

2023-06-21 | GSE209974 | GEO

LY6E impairs coronavirus fusion and confers immune control of viral disease.

Project description:Zoonotic coronaviruses (CoVs) are substantial threats to global health, as exemplified by the emergence of two severe acute respiratory syndrome CoVs (SARS-CoV and SARS-CoV-2) and Middle East respiratory syndrome CoV (MERS-CoV) within two decades1-3. Host immune responses to CoVs are complex and regulated in part through antiviral interferons. However, interferon-stimulated gene products that inhibit CoVs are not well characterized4. Here, we show that lymphocyte antigen 6 complex, locus E (LY6E) potently restricts infection by multiple CoVs, including SARS-CoV, SARS-CoV-2 and MERS-CoV. Mechanistic studies revealed that LY6E inhibits CoV entry into cells by interfering with spike protein-mediated membrane fusion. Importantly, mice lacking Ly6e in immune cells were highly susceptible to a murine CoV-mouse hepatitis virus. Exacerbated viral pathogenesis in Ly6e knockout mice was accompanied by loss of hepatic immune cells, higher splenic viral burden and reduction in global antiviral gene pathways. Accordingly, we found that constitutive Ly6e directly protects primary B cells from murine CoV infection. Our results show that LY6E is a critical antiviral immune effector that controls CoV infection and pathogenesis. These findings advance our understanding of immune-mediated control of CoV in vitro and in vivo-knowledge that could help inform strategies to combat infection by emerging CoVs.

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LY6E is a pan-coronavirus restriction factor in the respiratory tract

Project description:LY6E is a pan-coronavirus restriction factor in the respiratory tract

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Role of LY6E subpopulation on myeloma cell growth

Project description:Overexpression of LY6E in myeloma cells is associated with poor prognostic. We studied the molecular properties of LY6E+ and LY6E- myeloma cells from the same patients and assessed their growth potential

2024-05-01 | GSE233740 | GEO

Gene expression of LY6E-silent THP-1 cells and control THP-1 cells

Project description:Expression profiling of LY6E-silent THP-1 cells (THP-1-shLY6E) and control cells (THP-1-shCtrl). Results provide evidence that LY6E is effectively knocked down in THP-1shLY6E, compared to THP-1-shCtrl, and show the different expressed genes following LY6E silence in THP-1 cells. Total RNA obtained from 2 cell lines.

2014-09-06 | E-GEOD-44794 | biostudies-arrayexpress

Gene expression of LY6E-silent THP-1 cells and control THP-1 cells

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Seclidemstat blocks the transcriptional function of multiple FET-fusion oncoproteins

Project description:Seclidemstat blocks the transcriptional function of multiple FET-fusion oncoproteins

| PRJNA1111932 | ENA

Transcriptional profile of human STAT1-/- fibroblasts expressing LY6E or empty control vector

Project description:Detection of viral infection by pattern-recognition receptors triggers production of interferon. Secreted interferon binds to cognate receptors, triggering JAK/STAT signaling, resulting in the transcription and production of hundreds of interferon-stimulated genes (ISGs). Our lab identified lymphocyte antigen 6, locus E (LY6E) as an ISG that enhances infectivity of a subset of enveloped RNA viruses from Flaviviridae, Orthomyxoviridae, and Togaviridae families. To test whether the enhancing effects of LY6E were due to alterations of the global cellular transcriptome, we overexpressed LY6E and a control empty vector and examined global transcription using RNA-Seq.

2018-12-25 | GSE111958 | GEO

SARS coronavirus series

Project description:Set of microarray experiments used to identify an unknown coronavirus in a viral culture derived from a patient with SARS. March 2003. Keywords = SARS Keywords = coronavirus Keywords = viral discovery Keywords = viruses Keywords = respiratory infection

2010-06-05 | E-GEOD-546 | biostudies-arrayexpress

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