43 research outputs found
\u3cem\u3eTrichodysplasia Spinulosa\u3c/em\u3e-Associated Polyomavirus Uses a Displaced Binding Site on VP1 to Engage Sialylated Glycolipids
Trichodysplasia spinulosa-associated Polyomavirus (TSPyV) was isolated from a patient suffering from trichodysplasia spinulosa, a skin disease that can appear in severely immunocompromised patients. While TSPyV is one of the five members of the polyomavirus family that are directly linked to a human disease, details about molecular recognition events, the viral entry pathway, and intracellular trafficking events during TSPyV infection remain unknown. Here we have used a structure-function approach to shed light on the first steps of TSPyV infection. We established by cell binding and pseudovirus infection studies that TSPyV interacts with sialic acids during attachment and/or entry. Subsequently, we solved high-resolution X-ray structures of the major capsid protein VP1 of TSPyV in complex with three different glycans, the branched GM1 glycan, and the linear trisaccharides α2,3- and α2,6-sialyllactose. The terminal sialic acid of all three glycans is engaged in a unique binding site on TSPyV VP1, which is positioned about 18 Å from established sialic acid binding sites of other polyomaviruses. Structure-based mutagenesis of sialic acid-binding residues leads to reduction in cell attachment and pseudovirus infection, demonstrating the physiological relevance of the TSPyV VP1-glycan interaction. Furthermore, treatments of cells with inhibitors of N-, O-linked glycosylation, and glycosphingolipid synthesis suggest that glycolipids play an important role during TSPyV infection. Our findings elucidate the first molecular recognition events of cellular infection with TSPyV and demonstrate that receptor recognition by polyomaviruses is highly variable not only in interactions with sialic acid itself, but also in the location of the binding site
How society’s negative view of videogames can discourage brands from sponsoring eSports
The purpose of this research was to identify the main motives that contribute to society’s
negative view of videogames and that present a risk to the eSports sponsors’ image. To achieve
this, an exploratory, qualitative, and integrative literature review was conducted. According to
the theoretical data, there are four main reasons why society has a negative perception of
videogames. It is commonly believed that: (1) gaming is an unproductive activity, (2) violent
videogames incite aggressive behaviors, (3) videogames lead to gaming-addiction, and (4)
eSports lead to eSports-related gambling addiction. However, while the literature presents
convincing evidence that gaming can create addiction and that eSports can promote gambling
addiction, there is no conclusive evidence to assume that violent videogames lead to
aggressiveness and there is evidence showing that playing videogames can be a productive
activity. Nevertheless, these four beliefs are a threat to the eSports sponsors’ image and may
lead them to cancel their existing sponsorships or lead other brands to not want to sponsor
eSports to prevent being associated with these negative notions. This research will help expand
the minor literature on eSports sponsorships and advance the knowledge of why some eSports
sponsorships are terminated and why some brands may be reluctant to sponsor eSports.info:eu-repo/semantics/publishedVersio
Communicating on the edge of chaos : a transformation and change management perspective
'What is chaos, that we should be mindful of it?'
(Josepth Ford).
Chaos will always be a mystery. Perhaps the ultimate, allencompassing
mystery. To paraphrase Churchill's famous
remark, it is a paradox hidden inside a puzzle shrouded by
an enigma. It is visible proof of existence and uniqueness
without predictability.
In the Greco-Roman tradition philosophers used logic
and introspection to impose mental order on the universe.
Newton, Francis Bacon and the scientists of the Renaissance
chose a different path when attempting to find truth
and understanding nature. In the twentieth century Einstein,
Bohr and others (with quantum physics and mechanics)
changed the path again, making reality even more subtle
and complicated. Then, in the past twenty years, along came
chaos theory. This theory, and the ways that natural
processes move between order and disorder, brings us
closer to understanding the planetary orbits, the shape of
clouds, that phenomena never repeat themselves exactly,
and even the complexity of changing and learning
organisations. It is the insights and extensions of chaos
theory that could carry us technologically, philosophically,
socially and individually into the Age of Aquarius and
possibly through our own African Renaissance.
Most managers are naturally susceptible to wishful
thinking. They believe what they want to believe in spite of
obvious evidence to the contrary. They try to forcefully
manage and control to create balance and order in the
workplace. The time has arrived for South African business
leaders, managers and corporate communicators to buy into
the notion that a butterfly stirring the air in Johannesburg
can create a twister in New York!
This article describes chaos theory and examines how it
can be utilised to provide insights into managing and
communicating during times of change in chaotic
organisations
Trichodysplasia spinulosa-Associated Polyomavirus Uses a Displaced Binding Site on VP1 to Engage Sialylated Glycolipids
The Greater Affinity of JC Polyomavirus Capsid for alpha 2,6-Linked Lactoseries Tetrasaccharide c than for Other Sialylated Glycans Is a Major Determinant of Infectivity
Structural Basis and Evolution of Glycan Receptor Specificities within the Polyomavirus Family
ABSTRACT Asymptomatic infections with polyomaviruses in humans are common, but these small viruses can cause severe diseases in immunocompromised hosts. New Jersey polyomavirus (NJPyV) was identified via a muscle biopsy in an organ transplant recipient with systemic vasculitis, myositis, and retinal blindness, and human polyomavirus 12 (HPyV12) was detected in human liver tissue. The evolutionary origins and potential diseases are not well understood for either virus. In order to define their receptor engagement strategies, we first used nuclear magnetic resonance (NMR) spectroscopy to establish that the major capsid proteins (VP1) of both viruses bind to sialic acid in solution. We then solved crystal structures of NJPyV and HPyV12 VP1 alone and in complex with sialylated glycans. NJPyV employs a novel binding site for a α2,3-linked sialic acid, whereas HPyV12 engages terminal α2,3- or α2,6-linked sialic acids in an exposed site similar to that found in Trichodysplasia spinulosa-associated polyomavirus (TSPyV). Gangliosides or glycoproteins, featuring in mammals usually terminal sialic acids, are therefore receptor candidates for both viruses. Structural analyses show that the sialic acid-binding site of NJPyV is conserved in chimpanzee polyomavirus (ChPyV) and that the sialic acid-binding site of HPyV12 is widely used across the entire polyomavirus family, including mammalian and avian polyomaviruses. A comparison with other polyomavirus-receptor complex structures shows that their capsids have evolved to generate several physically distinct virus-specific receptor-binding sites that can all specifically engage sialylated glycans through a limited number of contacts. Small changes in each site may have enabled host-switching events during the evolution of polyomaviruses. IMPORTANCE Virus attachment to cell surface receptors is critical for productive infection. In this study, we have used a structure-based approach to investigate the cell surface recognition event for New Jersey polyomavirus (NJPyV) and human polyomavirus 12 (HPyV12). These viruses belong to the polyomavirus family, whose members target different tissues and hosts, including mammals, birds, fish, and invertebrates. Polyomaviruses are nonenveloped viruses, and the receptor-binding site is located in their capsid protein VP1. The NJPyV capsid features a novel sialic acid-binding site that is shifted in comparison to other structurally characterized polyomaviruses but shared with a closely related simian virus. In contrast, HPyV12 VP1 engages terminal sialic acids in a manner similar to the human Trichodysplasia spinulosa-associated polyomavirus. Our structure-based phylogenetic analysis highlights that even distantly related avian polyomaviruses possess the same exposed sialic acid-binding site. These findings complement phylogenetic models of host-virus codivergence and may also reflect past host-switching events
A structure-guided mutation in the major capsid protein retargets BK polyomavirus.
Viruses within a family often vary in their cellular tropism and pathogenicity. In many cases, these variations are due to viruses switching their specificity from one cell surface receptor to another. The structural requirements that underlie such receptor switching are not well understood especially for carbohydrate-binding viruses, as methods capable of structure-specificity studies are only relatively recently being developed for carbohydrates. We have characterized the receptor specificity, structure and infectivity of the human polyomavirus BKPyV, the causative agent of polyomavirus-associated nephropathy, and uncover a molecular switch for binding different carbohydrate receptors. We show that the b-series gangliosides GD3, GD2, GD1b and GT1b all can serve as receptors for BKPyV. The crystal structure of the BKPyV capsid protein VP1 in complex with GD3 reveals contacts with two sialic acid moieties in the receptor, providing a basis for the observed specificity. Comparison with the structure of simian virus 40 (SV40) VP1 bound to ganglioside GM1 identifies the amino acid at position 68 as a determinant of specificity. Mutation of this residue from lysine in BKPyV to serine in SV40 switches the receptor specificity of BKPyV from GD3 to GM1 both in vitro and in cell culture. Our findings highlight the plasticity of viral receptor binding sites and form a template to retarget viruses to different receptors and cell types