Targeting C-Type Lectin for the Treatment of Flavivirus Infections

Chen, Szu Ting; Lin, Yi-Ling; Huang, Ming Ting; Wu, Ming; Hsieh, Shie Liang

doi:10.1007/978-1-4419-7877-6_40

Cited by 4 publications

(3 citation statements)

References 23 publications

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“…Moreover, DV is able to activate NALP3 inflammasome via CLEC5A to secrete IL-1β, IL-18, and other proinflammatory cytokines from GM-CSF-induced inflammatory macrophages [6, 7]. All the evidence suggests that CLEC5A is a critical factor for the pathogenesis of flavivirus-induced systemic inflammatory reactions [8]. …”

Section: Introductionmentioning

confidence: 99%

CLEC5A is critical for dengue virus-induced osteoclast activation and bone homeostasis

Huang¹,

Chen

Liu

et al. 2016

J Mol Med

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Osteoclasts are bone tissue macrophages critical to maintain bone homeostasis. However, whether osteoclasts are susceptible to flaviviral infections and involved in dengue virus (DV)-induced disease pathogenesis is still unknown. In this study, we found that osteoclasts were preferentially susceptible to DV infection and produced similar amounts of cytokines and infectious virions as macrophages. Interestingly, DV-induced cytokine secretion and nuclear translocation of the transcription factor NFATc1 in osteoclast via the Syk-coupled myeloid C-type lectin member 5A (CLEC5A). Moreover, DV caused transient inflammatory reaction in bone tissue and upregulated osteolytic activity to release C-telopeptide of type I collagen (CTX-1) from bone tissue. Furthermore, DV-induced osteolytic activity was attenuated in CLEC5A-deficient mice, and administration of antagonistic anti-CLEC5A mAb inhibited DV-activated osteolytic activity and reduced CTX-1 serum level in vivo. This observation suggests that osteoclasts serve as a novel target for DV, and transient upregulation of osteolytic activity may contribute to the clinical symptoms in dengue patients.Key messagesCultured osteoclasts were susceptible to DV infection.Osteoclasts produced similar amounts of cytokines and infectious virions as macrophages.DV induced nuclear translocation of NFATc1 in osteoclast via CLEC5A.DV caused transient inflammatory reaction in bone tissue and upregulated osteolytic activity.Antagonistic anti-CLEC5A mAb inhibited DV-activated osteolytic activity in vivo.Electronic supplementary materialThe online version of this article (doi:10.1007/s00109-016-1409-0) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

CLEC5A is critical for dengue virus-induced osteoclast activation and bone homeostasis

Huang¹,

Chen

Liu

et al. 2016

J Mol Med

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“…Interactions of tetraspanins with pattern-recognition receptors (PRRs) have provided novel insights into the organization of Ag receptors in modulation of downstream signaling pathways (76). The Ctype Lectins receptors (LARs) are promising candidates for recognizing pathogen associated molecular patterns (PAMPs), and direct targeting of these LARs is commonly used as effective strategy to treat flaviviral infections (77). Tetraspanins collaborates with C-type Lectins to enhance viral attachment to cells and thus facilitates flavivirus infection (78).…”

Section: Tetraspanins Modulate Immune Responses and Related Mechanism(s)mentioning

confidence: 99%

Tetraspanins as Potential Therapeutic Candidates for Targeting Flaviviruses

2021

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Tetraspanin family of proteins participates in numerous fundamental signaling pathways involved in viral transmission, virus-specific immunity, and virus-mediated vesicular trafficking. Studies in the identification of novel therapeutic candidates and strategies to target West Nile virus, dengue and Zika viruses are highly warranted due to the failure in development of vaccines. Recent evidences have shown that the widely distributed tetraspanin proteins may provide a platform for the development of novel therapeutic approaches. In this review, we discuss the diversified and important functions of tetraspanins in exosome/extracellular vesicle biology, virus-host interactions, virus-mediated vesicular trafficking, modulation of immune mechanism(s), and their possible role(s) in host antiviral defense mechanism(s) through interactions with noncoding RNAs. We also highlight the role of tetraspanins in the development of novel therapeutics to target arthropod-borne flaviviral diseases.

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“…Human C-type lectin domain family 5 member A (CLEC5A), also known as myeloid DAP12-associating lectin-1 (MDL-1), is a II-type transmembrane protein and only expresses on the myeloid lineages including macrophages, monocytes, neutrophiles, and dendritic cells (DCs) (5)(6)(7). As a pattern recognition receptor, CLEC5A transmits signals into cytoplasm through non-covalent binding to the adaptor protein DAP12 (8).…”

Section: Introductionmentioning

confidence: 99%

A Pan-Cancer Analysis Reveals CLEC5A as a Biomarker for Cancer Immunity and Prognosis

Chen

et al. 2022

Front. Immunol.

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BackgroundCLEC5A is a member of the C-type lectin superfamily. It can activate macrophages and lead to a series of immune-inflammation reactions. Previous studies reveal the role of CLEC5A in infection and inflammation diseases.MethodWe acquire and analyze data from The Cancer Genome Atlas (TCGA) database, Genotype-Tissue Expression (GTEx) database, and other comprehensive databases via GSCALite, cBioPortal, and TIMER 2.0 platforms or software. Single-cell sequencing analysis was performed for quantifying the tumor microenvironment of several types of cancers.ResultsCLEC5A is differentially expressed in a few cancer types, of which overexpression accompanies low overall survival of patients. DNA methylation mainly negatively correlates with CLEC5A expression. Moreover, CLEC5A is positively related to immune infiltration, including macrophages, cancer-associated fibroblasts (CAFs), and regulatory T cells (Tregs). Immune checkpoint genes are significantly associated with CLEC5A expression in diverse cancers. In addition, CLEC5A expression correlates with mismatch repair (MMR) in several cancers. Tumor mutation burden (TMB), microsatellite instability (MSI), and neoantigens show a positive association with CLEC5A expression in several cancers. Furthermore, CLEC5A in cancer correlates with signal transduction, the immune system, EMT, and apoptosis process. The drug sensitivity analysis screens out potential therapeutic agents associated with CLEC5A expression, including FR-180204, Tivozanib, OSI-930, Linifanib, AC220, VNLG/124, Bexarotene, omacetaxine mepesuccinate, narciclasine, leptomycin B, PHA-793887, LRRK2-IN-1, and CR-1-31B.ConclusionCLEC5A overexpresses in multiple cancers in contrast to normal tissues, and high CLEC5A expression predicts poor prognosis of patients and immune infiltration. CLEC5A is a potential prognostic biomarker of diverse cancers and a target for anti-tumor therapy.

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Targeting C-Type Lectin for the Treatment of Flavivirus Infections

Cited by 4 publications

References 23 publications

CLEC5A is critical for dengue virus-induced osteoclast activation and bone homeostasis

CLEC5A is critical for dengue virus-induced osteoclast activation and bone homeostasis

Tetraspanins as Potential Therapeutic Candidates for Targeting Flaviviruses

A Pan-Cancer Analysis Reveals CLEC5A as a Biomarker for Cancer Immunity and Prognosis

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