Tetraspanin CD81 regulates HSV-1 infection

Benayas, Beatriz; Sastre, Isabel; López-Martín, Sara; Oo, Adrian; Kim, Baek; Bullido, María J.; Aldudo, Jesús; Yáñez-Mó, Marı́a

doi:10.1007/s00430-020-00684-0

Cited by 14 publications

(8 citation statements)

References 49 publications

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“…Since IIH is a benign disorder associated with high pressure in the brain, the immune cells derived from the CSF of patients with IIH were used as controls to compare Neuro-COVID. The cluster of differentiation molecule 81 (CD81) is one of the commonly regulated genes in the meta clusters of immune cells from the CSF of patients with Neuro-COVID and belongs to the tetraspanin superfamily, which has been shown to regulate viral entry, viral replication, infectivity, and virion exit of different types of viruses ( Benayas et al, 2020 ). Therefore, it is essential to investigate the importance of CD81 in patients with COVID-19 and Neuro-COVID.…”

Section: Discussionmentioning

confidence: 99%

Identification of Novel Gene Signatures using Next-Generation Sequencing Data from COVID-19 Infection Models: Focus on Neuro-COVID and Potential Therapeutics

2021

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SARS-CoV-2 is the causative agent for coronavirus disease-19 (COVID-19) and belongs to the family Coronaviridae that causes sickness varying from the common cold to more severe illnesses such as severe acute respiratory syndrome, sudden stroke, neurological complications (Neuro-COVID), multiple organ failure, and mortality in some patients. The gene expression profiles of COVID-19 infection models can be used to decipher potential therapeutics for COVID-19 and related pathologies, such as Neuro-COVID. Here, we used the raw RNA-seq reads (Single-End) in quadruplicates derived using Illumina Next Seq 500 from SARS-CoV-infected primary human bronchial epithelium (NHBE) and mock-treated NHBE cells obtained from the Gene Expression Omnibus (GEO) (GSE147507), and the quality control (QC) was evaluated using the CLC Genomics Workbench 20.0 (Qiagen, United States) before the RNA-seq analysis using BioJupies web tool and iPathwayGuide for gene ontologies (GO), pathways, upstream regulator genes, small molecules, and natural products. Additionally, single-cell transcriptomics data (GSE163005) of meta clusters of immune cells from the cerebrospinal fluid (CSF), such as T-cells/natural killer cells (NK) (TcMeta), dendritic cells (DCMeta), and monocytes/granulocyte (monoMeta) cell types for comparison, namely, Neuro-COVID versus idiopathic intracranial hypertension (IIH), were analyzed using iPathwayGuide. L1000 fireworks display (L1000FWD) and L1000 characteristic direction signature search engine (L1000 CDS2) web tools were used to uncover the small molecules that could potentially reverse the COVID-19 and Neuro-COVID-associated gene signatures. We uncovered small molecules such as camptothecin, importazole, and withaferin A, which can potentially reverse COVID-19 associated gene signatures. In addition, withaferin A, trichostatin A, narciclasine, camptothecin, and JQ1 have the potential to reverse Neuro-COVID gene signatures. Furthermore, the gene set enrichment analysis (GSEA) preranked method and Metascape web tool were used to decipher and annotate the gene signatures that were potentially reversed by these small molecules. In conclusion, our study unravels a rapid approach for applying next-generation knowledge discovery (NGKD) platforms to discover small molecules with therapeutic potential against COVID-19 and its related disease pathologies.

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Section: Discussionmentioning

confidence: 99%

Identification of Novel Gene Signatures using Next-Generation Sequencing Data from COVID-19 Infection Models: Focus on Neuro-COVID and Potential Therapeutics

2021

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“…There is a well-defined cholesterol-binding pocket which is important to tune the conformation of the protein and exploited by certain viruses to enter into cells. CD81 serves as co-receptor for many viruses, including the hepatitis C virus (HCV), human immunodeficiency virus type 1 (HIV-1), herpes simplex virus 1 (HSV-1), influenza A virus (IAV), Chikungunya virus and a few others [ 4 , 33 , 34 , 35 , 36 ], and occasionally for certain bacteria, such as Listeria monocytogenes [ 37 , 38 ], and tropical parasites, such as Plasmodium yoelii [ 39 ] ( Figure 2 ). The role of CD81 in HCV infection has been largely investigated.…”

Section: Cd81 Structure and Dynamic Architecturementioning

confidence: 99%

Targeting of Tetraspanin CD81 with Monoclonal Antibodies and Small Molecules to Combat Cancers and Viral Diseases

Bailly

Thuru

2023

Cancers

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Tetraspanin CD81 plays major roles in cell-cell interactions and the regulation of cellular trafficking. This cholesterol-embarking transmembrane protein is a co-receptor for several viruses, including HCV, HIV-1 and Chikungunya virus, which exploits the large extracellular loop EC2 for cell entry. CD81 is also an anticancer target implicated in cancer cell proliferation and mobility, and in tumor metastasis. CD81 signaling contributes to the development of solid tumors (notably colorectal, liver and gastric cancers) and has been implicated in the aggressivity of B-cell lymphomas. A variety of protein partners can interact with CD81, either to regulate attachment and uptake of viruses (HCV E2, claudin-1, IFIM1) or to contribute to tumor growth and dissemination (CD19, CD44, EWI-2). CD81-protein interactions can be modulated with molecules targeting the extracellular domain of CD81, investigated as antiviral and/or anticancer agents. Several monoclonal antibodies anti-CD81 have been developed, notably mAb 5A6 active against invasion and metastasis of triple-negative breast cancer cells. CD81-EC2 can also be targeted with natural products (trachelogenin and harzianoic acids A-B) and synthetic compounds (such as benzothiazole-quinoline derivatives). They are weak CD81 binders but offer templates for the design of new compounds targeting the open EC2 loop. There is no anti-CD81 compound in clinical development at present, but this structurally well-characterized tetraspanin warrants more substantial considerations as a drug target.

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“…Tspan26 is a B-cell surface antigen widely expressed on mature B cells, and it is involved in immune regulation and tumor suppression ( Xu-Monette et al, 2016 ). Tspan28 (CD81) knockout cells show impaired viral DNA replication and produce greatly diminished viral titers in Herpes simplex virus 1 infection in a neuroblastoma cell model ( Benayas et al, 2020 ).…”

Section: Physiological Functions Of Tetraspaninsmentioning

confidence: 99%

Tetraspanins as Potential Modulators of Glutamatergic Synaptic Function

Becic

Leifeld

Shaukat

et al. 2022

Front. Mol. Neurosci.

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Tetraspanins (Tspans) comprise a membrane protein family structurally defined by four transmembrane domains and intracellular N and C termini that is found in almost all cell types and tissues of eukaryotes. Moreover, they are involved in a bewildering multitude of diverse biological processes such as cell adhesion, motility, protein trafficking, signaling, proliferation, and regulation of the immune system. Beside their physiological roles, they are linked to many pathophysiological phenomena, including tumor progression regulation, HIV-1 replication, diabetes, and hepatitis. Tetraspanins are involved in the formation of extensive protein networks, through interactions not only with themselves but also with numerous other specific proteins, including regulatory proteins in the central nervous system (CNS). Interestingly, recent studies showed that Tspan7 impacts dendritic spine formation, glutamatergic synaptic transmission and plasticity, and that Tspan6 is correlated with epilepsy and intellectual disability (formerly known as mental retardation), highlighting the importance of particular tetraspanins and their involvement in critical processes in the CNS. In this review, we summarize the current knowledge of tetraspanin functions in the brain, with a particular focus on their impact on glutamatergic neurotransmission. In addition, we compare available resolved structures of tetraspanin family members to those of auxiliary proteins of glutamate receptors that are known for their modulatory effects.

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Tetraspanin CD81 regulates HSV-1 infection

Cited by 14 publications

References 49 publications

Identification of Novel Gene Signatures using Next-Generation Sequencing Data from COVID-19 Infection Models: Focus on Neuro-COVID and Potential Therapeutics

Identification of Novel Gene Signatures using Next-Generation Sequencing Data from COVID-19 Infection Models: Focus on Neuro-COVID and Potential Therapeutics

Targeting of Tetraspanin CD81 with Monoclonal Antibodies and Small Molecules to Combat Cancers and Viral Diseases

Tetraspanins as Potential Modulators of Glutamatergic Synaptic Function

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