BK Polyomavirus Infection of Bladder Microvascular Endothelial Cells Leads to the Activation of the cGAS-STING Pathway.

BK polyomavirus (BKPyV) infection in humans is usually asymptomatic but ultimately results in viral persistence. In immunocompromised hosts, virus reactivation can lead to nephropathy or hemorrhagic cystitis. The urinary tract serves as a silent reservoir for the virus.

Mouse polyomavirus infection induces lamin reorganisation.

The nuclear lamina is a dense network of intermediate filaments beneath the inner nuclear membrane. Composed of A-type lamins (lamin A/C) and B-type lamins (lamins B1 and B2), the nuclear lamina provides a scaffold for the nuclear envelope and chromatin, thereby maintaining the structural integrity of the nucleus. A-type lamins are also found inside the nucleus where they interact with chromatin and participate in gene regulation.

The interactions between PML nuclear bodies and small and medium size DNA viruses.

Promyelocytic leukemia nuclear bodies (PM NBs), often referred to as membraneless organelles, are dynamic macromolecular protein complexes composed of a PML protein core and other transient or permanent components. PML NBs have been shown to play a role in a wide variety of cellular processes. This review describes in detail the diverse and complex interactions between small and medium size DNA viruses and PML NBs that have been described to date.

The Interplay between Viruses and Host DNA Sensors.

DNA virus infections are often lifelong and can cause serious diseases in their hosts. Their recognition by the sensors of the innate immune system represents the front line of host defence. Understanding the molecular mechanisms of innate immunity responses is an important prerequisite for the design of effective antivirotics.

Nuclear Cytoskeleton in Virus Infection.

The nuclear lamina is the main component of the nuclear cytoskeleton that maintains the integrity of the nucleus. However, it represents a natural barrier for viruses replicating in the cell nucleus. The lamina blocks viruses from being trafficked to the nucleus for replication, but it also impedes the nuclear egress of the progeny of viral particles.

VirPorters: Insights into the action of cationic and histidine-rich cell-penetrating peptides.

The utilization of nanoparticles for the intracellular delivery of theranostic agents faces one substantial limitation. Sequestration in intracellular vesicles prevents them from reaching the desired location in the cytoplasm or nucleus to deliver their cargo. We investigated whether three different cell-penetrating peptides (CPPs), namely, octa-arginine R8, polyhistidine KH27K and histidine-rich LAH4, could promote cytosolic and/or nuclear transfer of unique model nanoparticles-pseudovirions derived from murine polyomavirus.

Immune sensing of mouse polyomavirus DNA by p204 and cGAS DNA sensors.

The mechanism by which DNA viruses interact with different DNA sensors and their connection with the activation of interferon (IFN) type I pathway are poorly understood. We investigated the roles of protein 204 (p204) and cyclic guanosine-adenosine synthetase (cGAS) sensors during infection with mouse polyomavirus (MPyV). The phosphorylation of IFN regulatory factor 3 (IRF3) and the stimulator of IFN genes (STING) proteins and the upregulation of IFN beta (IFN-β) and MX Dynamin Like GTPase 1 (MX-1) genes were detected at the time of replication of MPyV genomes in the nucleus.

TLR4-Mediated Recognition of Mouse Polyomavirus Promotes Cancer-Associated Fibroblast-Like Phenotype and Cell Invasiveness.

The tumorigenic potential of mouse polyomavirus (MPyV) has been studied for decades in cell culture models and has been mainly attributed to nonstructural middle T antigen (MT), which acts as a scaffold signal adaptor, activates Src tyrosine kinases, and possesses transforming ability. We hypothesized that MPyV could also transform mouse cells independent of MT via a Toll-like receptor 4 (TLR4)-mediated inflammatory mechanism. To this end, we investigated the interaction of MPyV with TLR4 in mouse embryonic fibroblasts (MEFs) and 3T6 cells, resulting in secretion of interleukin 6 (IL-6), independent of active viral replication.

The Protein Corona Does Not Influence Receptor-Mediated Targeting of Virus-like Particles.

Protein corona formation has been regarded as an obstacle to developing diagnostic and therapeutic nanoparticles for applications. Serum proteins that assemble around nanoparticles can hinder their targeting efficiency. Virus-based nanoparticles should be naturally predisposed to evade such barriers in host organisms.

The Major Capsid Protein, VP1, of the Mouse Polyomavirus Stimulates the Activity of Tubulin Acetyltransferase 1 by Microtubule Stabilization.

Viruses have evolved mechanisms to manipulate microtubules (MTs) for the efficient realization of their replication programs. Studying the mechanisms of replication of mouse polyomavirus (MPyV), we observed previously that in the late phase of infection, a considerable amount of the main structural protein, VP1, remains in the cytoplasm associated with hyperacetylated microtubules. VP1-microtubule interactions resulted in blocking the cell cycle in the G2/M phase.

Microtubules in Polyomavirus Infection.

Microtubules, part of the cytoskeleton, are indispensable for intracellular movement, cell division, and maintaining cell shape and polarity. In addition, microtubules play an important role in viral infection. In this review, we summarize the role of the microtubules' network during polyomavirus infection.

Influence of cell-penetrating peptides on the activity and stability of virus-based nanoparticles.

Viral nanoparticles represent potential natural versatile platforms for targeted gene and drug delivery. Improving the efficiency of gene transfer mediated by viral vectors could not only enhance their therapeutic potential, but also contribute to understanding the limitations in interactions of nanoparticles with cells and the development of new therapeutic approaches. In this study, four cell-penetrating peptides (CPPs), cationic octaarginine (R8), histidine-rich peptides (LAH4 and KH27K) and fusogenic peptide (FUSO), are investigated for their effect on infection by mouse polyomavirus (MPyV) or on transduction of reporter genes delivered by MPyV or related viral vectors.

Prevalence of antibodies against BKPyV subtype I and IV in kidney transplant recipients and in the general Czech population.

Active infection with BK polyomavirus (BKPyV) may cause serious complications in transplantation settings. Recently, the level of BKPyV IgG seroreactivity in graft donors has been shown to predict viremia and BKPyV-associated nephropathy in kidney transplant (KTx) recipients. Pretransplantation testing of the donor and recipient BKPyV serostatus could, therefore, identify patients at high risk.

Interaction of the Mouse Polyomavirus Capsid Proteins with Importins Is Required for Efficient Import of Viral DNA into the Cell Nucleus.

The mechanism used by mouse polyomavirus (MPyV) overcomes the crowded cytosol to reach the nucleus has not been fully elucidated. Here, we investigated the involvement of importin α/β1 mediated transport in the delivery of MPyV genomes into the nucleus. Interactions of the virus with importin β1 were studied by co-immunoprecipitation and proximity ligation assay.

Exploitation of stable nanostructures based on the mouse polyomavirus for development of a recombinant vaccine against porcine circovirus 2.

The aim of this study was to develop a suitable vaccine antigen against porcine circovirus 2 (PCV2), the causative agent of post-weaning multi-systemic wasting syndrome, which causes significant economic losses in swine breeding. Chimeric antigens containing PCV2b Cap protein sequences based on the mouse polyomavirus (MPyV) nanostructures were developed. First, universal vectors for baculovirus-directed production of chimeric MPyV VLPs or pentamers of the major capsid protein, VP1, were designed for their exploitation as vaccines against other pathogens.

Hydrophobic domains of mouse polyomavirus minor capsid proteins promote membrane association and virus exit from the ER.

The minor structural protein VP2 and its shorter variant, VP3, of mouse polyomavirus (MPyV) are essential for virus exit from the endoplasmic reticulum (ER) during viral trafficking to the nucleus. Here, we followed the role of putative hydrophobic domains (HD) of the minor proteins in membrane affinity and viral infectivity. We prepared variants of VP2, each mutated to decrease hydrophobicity of one of three predicted hydrophobic domains: VP2-mHD1, VP2-mHD2 or VP2-mHD3 mutated in HD1 (amino acids (aa) 60-101), HD2 (aa 125-165) or HD3 (aa 287-307), respectively.

Retargeting Polyomavirus-Like Particles to Cancer Cells by Chemical Modification of Capsid Surface.

Virus-like particles based on polyomaviruses (PVLPs) are promising delivery devices for various cargoes, including nucleic acids, imaging probes, and therapeutic agents. In biological environments, the major coat protein VP1 interacts with ubiquitously distributed sialic acid residues, and therefore PVLPs show a broad tropism. For selective targeting, appropriate engineering of the PVLP surface is needed.

VP1, the major capsid protein of the mouse polyomavirus, binds microtubules, promotes their acetylation and blocks the host cell cycle.

VP1, the major structural protein of the mouse polyomavirus (MPyV), is the major architectural component of the viral capsid. Its pentamers are able to self-assemble into capsid-like particles and to non-specifically bind DNA. Surface loops of the protein interact with sialic acid of ganglioside receptors.

Antibacterial, Antiviral, and Oxygen-Sensing Nanoparticles Prepared from Electrospun Materials.

A simple nanoprecipitation method was used for preparation of stable photoactive polystyrene nanoparticles (NPs, diameter 30 ± 10 nm) from sulfonated electrospun polystyrene nanofiber membranes with encapsulated 5,10,15,20-tetraphenylporphyrin (TPP) or platinum octaethylporphyrin (Pt-OEP). The NPs prepared with TPP have strong antibacterial and antiviral properties and can be applied to the photooxidation of external substrates based on photogenerated singlet oxygen. In contrast to nanofiber membranes, which have limited photooxidation ability near the surface, NPs are able to travel toward target species/structures.

Mouse Polyomavirus: Propagation, Purification, Quantification, and Storage.

Mouse polyomavirus (MPyV) is a member of the Polyomaviridae family, which comprises non-enveloped tumorigenic viruses infecting various vertebrates including humans and causing different pathogenic responses in the infected organisms. Despite the variations in host tropism and pathogenicity, the structure of the virions of these viruses is similar. The capsid, with icosahedral symmetry (ø, 45 nm, T = 7d), is composed of a shell of 72 capsomeres of structural proteins, arranged around the nucleocore containing approximately 5-kbp-long circular dsDNA in complex with cellular histones.

Coat as a dagger: the use of capsid proteins to perforate membranes during non-enveloped DNA viruses trafficking.

To get access to the replication site, small non-enveloped DNA viruses have to cross the cell membrane using a limited number of capsid proteins, which also protect the viral genome in the extracellular environment. Most of DNA viruses have to reach the nucleus to replicate. The capsid proteins involved in transmembrane penetration are exposed or released during endosomal trafficking of the virus.

Superhydrophilic polystyrene nanofiber materials generating O2((1)Δ(g)): postprocessing surface modifications toward efficient antibacterial effect.

The surfaces of electrospun polystyrene (PS) nanofiber materials with encapsulated 1% w/w 5,10,15,20-tetraphenylporphyrin (TPP) photosensitizer were modified through sulfonation, radio frequency (RF) oxygen plasma treatment, and polydopamine coating. The nanofiber materials exhibited efficient photogeneration of singlet oxygen. The postprocessing modifications strongly increased the wettability of the pristine hydrophobic PS nanofibers without causing damage to the nanofibers, leakage of the photosensitizer, or any substantial change in the oxygen permeability of the inner bulk of the polymer nanofiber.

Involvement of microtubular network and its motors in productive endocytic trafficking of mouse polyomavirus.

Infection of non-enveloped polyomaviruses depends on an intact microtubular network. Here we focus on mouse polyomavirus (MPyV). We show that the dynamics of MPyV cytoplasmic transport reflects the characteristics of microtubular motor-driven transport with bi-directional saltatory movements.

The encapsidation of polyomavirus is not defined by a sequence-specific encapsidation signal.

Mouse polyomavirus (MPyV) is considered a potential tool for the application of gene therapy; however, the current knowledge of the encapsulation of DNA into virions is vague. We used a series of assays based on the encapsidation of a reporter vector into MPyV pseudovirions to identify putative cis-acting elements that are involved in DNA encapsidation. None of the sequences that were derived from MPyV have been shown to solely enhance the encapsidation of a reporter vector in the assay.