A novel neuropilin-1–binding sequence in the human T-cell lymphotropic virus type 1 envelope glycoprotein

Kusunoki, Hideki; Tanaka, Toŝhiyuki; Kohno, Toshiyuki; Matsuhashi, Kazuhiko; Hosoda, Kazuo; Wakamatsu, Kaori; Hamaguchi, Isao

doi:10.1016/j.bbapap.2018.02.003

Cited by 4 publications

(3 citation statements)

References 44 publications

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“…Among them, antiviral response was the most significantly affected annotation sorted by | z-score|. There is a growing appreciation for roles played by NRP1 in the immune response, especially in the function of regulatory T cell response to virus infection ( 35 , 36 ). In fact, investigations of the possible correlation between infection with different viruses, including human papilloma virus (HPV), human immunodeficiency virus (HIV), polyomavirus (BK) virus, herpes simplex virus, human T cell lymphotropic virus type 1 (HTLV-1), or Epstein-Barr virus (EBV), and the occurrence of BC are underway ( 37 , 38 ).…”

Section: Discussionmentioning

confidence: 99%

“…Although the association between NRP1 and HPV remains elusive, HIV could lead to upregulation of NRP1 and suppress the expression of semaphorin 3a in the podocyte ( 40 ), while inhibiting VEGF from binding to NRP1 in endothelial cells to block angiogenesis and induce apoptosis ( 41 ). Besides, the NRP1 contains domains that directly interact with HTLV-1 ( 36 ) and EBV ( 42 ). Furthermore, NRP1 is identified as an EBV entry factor, its overexpression enhances EBV infection in nasopharyngeal epithelial cells ( 42 ), and highly expressed NRP1 could be consider as an undesirable independent prognostic factor in EBV-associated lymphomas ( 43 ).…”

Section: Discussionmentioning

confidence: 99%

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Role of NRP1 in Bladder Cancer Pathogenesis and Progression

Dong

Zhang

et al. 2021

Front. Oncol.

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Bladder urothelial carcinoma (BC) is a fatal invasive malignancy and the most common malignancy of the urinary system. In the current study, we investigated the function and mechanisms of Neuropilin-1 (NRP1), the co-receptor for vascular endothelial growth factor, in BC pathogenesis and progression. The expression of NRP1 was evaluated using data extracted from GEO and HPA databases and examined in BC cell lines. The effect on proliferation, apoptosis, angiogenesis, migration, and invasion of BC cells were validated after NRP1 knockdown. After identifying differentially expressed genes (DEGs) induced by NRP1 silencing, GO/KEGG and IPA® bioinformatics analyses were performed and specific predicted pathways and targets were confirmed in vitro. Additionally, the co-expressed genes and ceRNA network were predicted using data downloaded from CCLE and TCGA databases, respectively. High expression of NRP1 was observed in BC tissues and cells. NRP1 knockdown promoted apoptosis and suppressed proliferation, angiogenesis, migration, and invasion of BC cells. Additionally, after NRP1 silencing the activity of MAPK signaling and molecular mechanisms of cancer pathways were predicted by KEGG and IPA® pathway analysis and validated using western blot in BC cells. NRP1 knockdown also affected various biological functions, including antiviral response, immune response, cell cycle, proliferation and migration of cells, and neovascularisation. Furthermore, the main upstream molecule of the DEGs induced by NRP1 knockdown may be NUPR1, and NRP1 was also the downstream target of NUPR1 and essential for regulation of FOXP3 expression to activate neovascularisation. DCBLD2 was positively regulated by NRP1, and PPAR signaling was significantly associated with low NRP1 expression. We also found that NRP1 was a predicted target of miR-204, miR-143, miR-145, and miR-195 in BC development. Our data provide evidence for the biological function and molecular aetiology of NRP1 in BC and for the first time demonstrated an association between NRP1 and NUPR1, FOXP3, and DCBLD2. Specifically, downregulation of NRP1 contributes to BC progression, which is associated with activation of MAPK signaling and molecular mechanisms involved in cancer pathways. Therefore, NRP1 may serve as a target for new therapeutic strategies to treat BC and other cancers.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Role of NRP1 in Bladder Cancer Pathogenesis and Progression

Dong

Zhang

et al. 2021

Front. Oncol.

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“…First, the viral surface unit attaches to the heparin/heparan sulfate proteoglycan (HSPG) on the host cell surface. Then the HSPG/virus surface complex interacts with the b1 domain of NRP1, which triggers conformational changes of the viral surface that enable its interaction with glucose transporter GLUT-1, yielding HTLV-1 fusion and cell entry [ 50 ].…”

Section: Neuropilin-related Pathologymentioning

confidence: 99%

Neuropilin (NRPs) Related Pathological Conditions and Their Modulators

Broz

Kolarič

Jukič

et al. 2022

IJMS

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Neuropilin 1 (NRP1) represents one of the two homologous neuropilins (NRP, splice variants of neuropilin 2 are the other) found in all vertebrates. It forms a transmembrane glycoprotein distributed in many human body tissues as a (co)receptor for a variety of different ligands. In addition to its physiological role, it is also associated with various pathological conditions. Recently, NRP1 has been discovered as a coreceptor for the SARS-CoV-2 viral entry, along with ACE2, and has thus become one of the COVID-19 research foci. However, in addition to COVID-19, the current review also summarises its other pathological roles and its involvement in clinical diseases like cancer and neuropathic pain. We also discuss the diversity of native NRP ligands and perform a joint analysis. Last but not least, we review the therapeutic roles of NRP1 and introduce a series of NRP1 modulators, which are typical peptidomimetics or other small molecule antagonists, to provide the medicinal chemistry community with a state-of-the-art overview of neuropilin modulator design and NRP1 druggability assessment.

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Host Manipulation Mechanisms of SARS-CoV-2

Massey

2021

Acta Biotheor

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Viruses are the simplest of pathogens, but possess sophisticated molecular mechanisms to manipulate host behavior, frequently utilizing molecular mimicry. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been shown to bind to the host receptor neuropilin-1 in order to gain entry into the cell. To do this, the virus utilizes its spike protein polybasic cleavage site (PCS), which mimics the CendR motif of neuropilin-1’s endogenous ligands. In addition to facilitating cell entry, binding to neuropilin-1 has analgesic effects. We discuss the potential impact of neuropilin-1 binding by SARS-CoV-2 in ameliorating sickness behavior of the host, and identify a convergent evolutionary strategy of PCS cleavage and subsequent neuropilin binding in other human viruses. In addition, we discuss the evolutionary leap of the ancestor of SARS-COV-2, which involved acquisition of the PCS thus faciliting binding to the neuropilin-1 receptor. Acquisition of the PCS by the ancestor of SARS-CoV-2 appears to have led to pleiotropic beneficial effects including enhancement of cell entry via binding to ACE2, facilitation of cell entry via binding to neuropilin-1, promotion of analgesia, and potentially the formation of decoy epitopes via enhanced shedding of the S1 subunit. Lastly, other potential neuromanipulation strategies employed by SARS-CoV-2 are discussed, including interferon suppression and the resulting reduction in sickness behavior, enhanced transmission through neurally mediated cough induction, and reduction in sense of smell.

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A novel neuropilin-1–binding sequence in the human T-cell lymphotropic virus type 1 envelope glycoprotein

Cited by 4 publications

References 44 publications

Role of NRP1 in Bladder Cancer Pathogenesis and Progression

Role of NRP1 in Bladder Cancer Pathogenesis and Progression

Neuropilin (NRPs) Related Pathological Conditions and Their Modulators

Host Manipulation Mechanisms of SARS-CoV-2

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