White Blood Cell Membrane‐Coated Nanoparticles: Recent Development and Medical Applications

Advanced Healthcare Materials, Journal Year: 2021, Volume and Issue: 11(7)

Published: Aug. 31, 2021

White blood cells (WBCs) are immune that play essential roles in critical diseases including cancers, infections, and inflammatory disorders. Their dynamic diverse functions have inspired the development of WBC membrane-coated nanoparticles (denoted "WBC-NPs"), which formed by fusing plasma membranes WBCs, such as macrophages, neutrophils, T cells, natural killer onto synthetic nanoparticle cores. Inheriting entire source cell antigens, WBC-NPs act decoys simulate their broad biointerfacing properties with intriguing therapeutic potentials. Herein, recent medical applications focusing on four areas, carriers for drug delivery, countermeasures biological neutralization, nanovaccines modulation, tools isolation circulating tumor fundamental research is reviewed. Overall, studies established platform versatile nanotherapeutics application

Language: Английский

---

Liquid Biomolecular Condensates and Viral Lifecycles: Review and Perspectives

Viruses, Journal Year: 2021, Volume and Issue: 13(3), P. 366 - 366

Published: Feb. 25, 2021

Viruses are highly dependent on the host they infect. Their dependence triggers processes of virus-host co-adaptation, enabling viruses to explore resources whilst escaping immunity. Scientists have tackled viral-host interplay at differing levels complexity-in individual hosts, organs, tissues and cells-and seminal studies advanced our understanding about viral lifecycles, intra- or inter-species transmission, means control infections. Recently, it emerged as important address physical properties materials in biological systems; membrane-bound organelles only one many ways separate molecules from cellular milieu. By achieving a type compartmentalization lacking membranes known biomolecular condensates, systems developed alternative mechanisms controlling reactions. The identification that condensates display liquid led proposal liquid-liquid phase separation (LLPS) drives their formation. concept LLPS is paradigm shift structure organization. There an unprecedented momentum revisit long-standing questions virology novel antiviral strategies. In first part this review, we focus state-of-the-art condensates. second part, capture what RNA virus-phase biology discuss future perspectives emerging field virology.

Language: Английский

---

Co-option of endogenous viral sequences for host cell function

Current Opinion in Virology, Journal Year: 2017, Volume and Issue: 25, P. 81 - 89

Published: Aug. 1, 2017

Language: Английский

---

Physical properties of the HIV-1 capsid from all-atom molecular dynamics simulations

Nature Communications, Journal Year: 2017, Volume and Issue: 8(1)

Published: July 19, 2017

Abstract Human immunodeficiency virus type 1 (HIV-1) infection is highly dependent on its capsid. The capsid a large container, made of ∼1,300 proteins with altogether 4 million atoms. Although the are all identical, they nevertheless arrange themselves into largely asymmetric structure hexamers and pentamers. number degrees freedom lack symmetry pose challenge to studying chemical details HIV Simulations over 64 atoms for μs allow us conduct comprehensive study chemical–physical properties an empty HIV-1 capsid, including electrostatics, vibrational acoustic properties, effects solvent (ions water) simulations reveal critical about implications biological function.

Language: Английский

---

A highly potent long-acting small-molecule HIV-1 capsid inhibitor with efficacy in a humanized mouse model

Nature Medicine, Journal Year: 2019, Volume and Issue: 25(9), P. 1377 - 1384

Published: Sept. 1, 2019

Language: Английский

---

Low-dose phase retrieval of biological specimens using cryo-electron ptychography

Nature Communications, Journal Year: 2020, Volume and Issue: 11(1)

Published: June 2, 2020

Cryo-electron microscopy is an essential tool for high-resolution structural studies of biological systems. This method relies on the use phase contrast imaging at high defocus to improve information transfer low spatial frequencies expense higher frequencies. Here we demonstrate that electron ptychography can recover specimen with continuous across a wide range frequency spectrum, improved lower frequencies, and as such more efficient recovery than conventional imaging. We further show be used study frozen-hydrated specimens rotavirus double-layered particles HIV-1 virus-like under low-dose conditions (5.7 e/Å

Language: Английский

---

Structure and architecture of immature and mature murine leukemia virus capsids

Proceedings of the National Academy of Sciences, Journal Year: 2018, Volume and Issue: 115(50)

Published: Nov. 26, 2018

Retroviruses assemble and bud from infected cells in an immature form require proteolytic maturation for infectivity. The CA (capsid) domains of the Gag polyproteins a protein lattice as truncated sphere virion. Proteolytic cleavage induces dramatic structural rearrangements; subset cleaved subsequently assembles into mature core, whose architecture varies among retroviruses. Murine leukemia virus (MLV) is prototypical γ-retrovirus serves basis retroviral vectors, but structure MLV layer unknown. Here we have combined X-ray crystallography with cryoelectron tomography to determine structures layers within authentic viral particles. This reveals changes associated maturation, and, by comparison HIV-1, uncovers conserved variable features. In contrast most used assembly which adopts variable, multilayered morphologies does not closed structure. Unlike there similarity between protein–protein interfaces those layer, could be achieved through domain rotations that largely maintain hexameric interactions. Nevertheless, architectural change on indicates extensive disassembly reassembly are required core growth. morphology suggests wrapping genome sheets may sufficient protect ribonucleoprotein during cell entry.

Language: Английский

---

A lipid-based partitioning mechanism for selective incorporation of proteins into membranes of HIV particles

Nature Cell Biology, Journal Year: 2019, Volume and Issue: 21(4), P. 452 - 461

Published: April 1, 2019

Language: Английский

---

Ebselen, a Small-Molecule Capsid Inhibitor of HIV-1 Replication

Antimicrobial Agents and Chemotherapy, Journal Year: 2016, Volume and Issue: 60(4), P. 2195 - 2208

Published: Jan. 26, 2016

The human immunodeficiency virus type 1 (HIV-1) capsid plays crucial roles in HIV-1 replication and thus represents an excellent drug target. We developed a high-throughput screening method based on time-resolved fluorescence resonance energy transfer (HTS-TR-FRET) assay, using the C-terminal domain (CTD) of to identify inhibitors dimerization. This assay was used screen library pharmacologically active compounds, composed 1,280in vivo-active drugs, identified ebselen [2-phenyl-1,2-benzisoselenazol-3(2H)-one], organoselenium compound, as inhibitor CTD Nuclear magnetic (NMR) spectroscopic analysis confirmed direct interaction with dimer dissociation when is 2-fold molar excess. Electrospray ionization mass spectrometry revealed that covalently binds CTD, likely via selenylsulfide linkage Cys198 Cys218. compound presents anti-HIV activity single multiple rounds infection permissive cell lines well primary peripheral blood mononuclear cells. Ebselen inhibits early viral postentry events life cycle by impairing incoming uncoating process. also blocks other retroviruses, such Moloney murine leukemia simian virus, but displays no inhibitory against hepatitis C influenza viruses. study reports use TR-FRET successfully novel inhibitor, ebselen, validating promising target for development.

Language: Английский

---

HIV virions sense plasma membrane heterogeneity for cell entry

Science Advances, Journal Year: 2017, Volume and Issue: 3(6)

Published: June 2, 2017

HIV virions target co-receptors and fuse at ordered/disordered domain boundaries in cholesterol-rich plasma membranes.

Language: Английский

---