Intracellular Trafficking and Endocytic Uptake Pathway of Pepper Vein Banding Virus-Like Particles in Epithelial Cells

Sabharwal, Pallavi; Amritha, Chemmenchery K; Sushmitha, C.; Natraj, Usha; Savithri, H.S.

doi:10.2217/nnm-2018-0405

Cited by 8 publications

(6 citation statements)

References 74 publications

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“…Mannose-rich VLPs were also avidly bound and internalized by human monocyte-derived dendritic cells (moDCs) (Figure c). In the experiment, the sparsely mannosylated and control PE-decorated particles gave low but detectable signals, consistent with observations that a wide variety of protein nanoparticles can undergo receptor-mediated endocytosis and other processes such as macropinocytosis. − …”

Section: Resultssupporting

confidence: 84%

Glycan-Modified Virus-like Particles Evoke T Helper Type 1-like Immune Responses

et al. 2020

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Dendritic cells (DCs) are highly effective antigen-presenting cells that shape immune responses. Vaccines that deliver antigen to the DCs can harness their power. DC surface lectins recognize glycans not typically present on host tissue to facilitate antigen uptake and presentation. Vaccines that target these surface lectins should offer improved antigen delivery, but their efficacy will depend on how lectin targeting influences the T cell subtypes that result. We examined how antigen structure influences uptake and signaling from the C-type lectin DC-SIGN (dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin or CD209). Virus-like particles (VLPs) were engineered from bacteriophage Qβ to present an array of mannoside ligands. The VLPs were taken up by DCs and efficiently trafficked to endosomes. The signaling that ensued depended on the ligand displayed on the VLP: only those particles densely functionalized with an aryl mannoside, Qβ-Man540, elicited DC maturation and induced the expression of the proinflammatory cytokines characteristic of a T helper type 1 (TH1)-like immune response. This effect was traced to differential binding to DC-SIGN at the acidic pH of the endosome. Mice immunized with a VLP bearing the aryl mannoside, and a peptide antigen (Qβ-Ova-Man540) had antigen-specific responses, including the production of CD4+ T cells producing the activating cytokines interferon-γ and tumor necrosis factor-α. A TH1 response is critical for intracellular pathogens (e.g., viruses) and cancer; thus, our data highlight the value of targeting DC lectins for antigen delivery and validate the utility of DC-targeted VLPs as vaccine vehicles that induce cellular immunity.

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Section: Resultssupporting

confidence: 84%

Glycan-Modified Virus-like Particles Evoke T Helper Type 1-like Immune Responses

et al. 2020

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“…Our analysis from MD studies shows significant correlation with previously documented biochemical studies [13]. The biochemical experiments suggest that the protease activity of the NIa‐Pro mutants, Ser129Ala, Trp143Ala, His142Ala, and His167Ala are impaired compared to the wild type [60]. Our simulation studies indicate that the decrease in catalytic activity of the mutants could possibly be associated with a conformational change in the catalytic triad.…”

Section: Discussionsupporting

confidence: 82%

Mapping allosteric pathway in NIa‐Pro using computational approach

Panigrahi

Kailasam

2023

Quant. Biol.

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Background: Computer simulation studies complement in vitro experiments and provide avenue to understand allosteric regulation in the absence of other molecular viewing techniques. Molecular dynamics captures internal motion within the protein and enables tracing the communication path between a catalytic site and a distal allosteric site. In this article, we have identified the communication pathway between the viral protein genome linked (VPg) binding region and catalytic active site in nuclear inclusion protein-a protease (NIa-Pro). Methods: Molecular dynamics followed by in silico analyses have been used to map the allosteric pathway. Results: This study delineates the residue interaction network involved in allosteric regulation of NIa-Pro activity by VPg. Simulation studies indicate that point mutations in the VPg interaction interface of NIa-Pro lead to disruption in these networks and change the orientation of catalytic residues. His142Ala and His167Ala mutations do not show a substantial change in the overall protease structure, but rather in the residue interaction network and catalytic site geometry. Conclusion: Our mutagenic study delineates the allosteric pathway and facilitates the understanding of the modulation of NIa-Pro activity on a molecular level in the absence of the structure of its complex with the known regulator VPg. Additionally, our in silico analysis explains the molecular concepts and highlights the dynamics behind the previously reported wet lab study findings.

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“…Phosphorylation of Vimentin intermediate filaments at Ser459 by Polo-like kinase 1 (Plk1) inhibits the endolytic fusion during mitosis ( Ikawa et al, 2014 ). Altogether these interactions demonstrate vimentin as a critical regulator of late endocytic trafficking and egress of viral particles ( Risco et al, 2002 ; Fay and Pante, 2013 ; Wu and Pante, 2016 ; Sabharwal et al, 2019 ). In another strategy, African swine fever virus, Vaccinia virus, and Enterovirus trigger rearrangement of Vimentin intermediate filaments as cages around the viral replication factories ( Risco et al, 2002 ).…”

Section: Vimentin Intermediate Filaments In Pathological Roles In Lun...mentioning

confidence: 91%

Pathophysiological Role of Vimentin Intermediate Filaments in Lung Diseases

Surolia

Antony

2022

Front. Cell Dev. Biol.

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Vimentin intermediate filaments, a type III intermediate filament, are among the most widely studied IFs and are found abundantly in mesenchymal cells. Vimentin intermediate filaments localize primarily in the cytoplasm but can also be found on the cell surface and extracellular space. The cytoplasmic vimentin is well-recognized for its role in providing mechanical strength and regulating cell migration, adhesion, and division. The post-translationally modified forms of Vimentin intermediate filaments have several implications in host-pathogen interactions, cancers, and non-malignant lung diseases. This review will analyze the role of vimentin beyond just the epithelial to mesenchymal transition (EMT) marker highlighting its role as a regulator of host-pathogen interactions and signaling pathways for the pathophysiology of various lung diseases. In addition, we will also examine the clinically relevant anti-vimentin compounds and antibodies that could potentially interfere with the pathogenic role of Vimentin intermediate filaments in lung disease.

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Intracellular Trafficking and Endocytic Uptake Pathway of Pepper Vein Banding Virus-Like Particles in Epithelial Cells

Cited by 8 publications

References 74 publications

Glycan-Modified Virus-like Particles Evoke T Helper Type 1-like Immune Responses

Glycan-Modified Virus-like Particles Evoke T Helper Type 1-like Immune Responses

Mapping allosteric pathway in NIa‐Pro using computational approach

Pathophysiological Role of Vimentin Intermediate Filaments in Lung Diseases

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