Search results for "REPLICATION"

Herpes simplex virus 1 induces egress channels through marginalized host chromatin

2016

AbstractLytic infection with herpes simplex virus type 1 (HSV-1) induces profound modification of the cell nucleus including formation of a viral replication compartment and chromatin marginalization into the nuclear periphery. We used three-dimensional soft X-ray tomography, combined with cryogenic fluorescence, confocal and electron microscopy, to analyse the transformation of peripheral chromatin during HSV-1 infection. Our data showed an increased presence of low-density gaps in the marginalized chromatin at late infection. Advanced data analysis indicated the formation of virus-nucleocapsid-sized (or wider) channels extending through the compacted chromatin of the host. Importantly, co…

Famotidine inhibits toll-like receptor 3-mediated inflammatory signaling in SARS-CoV-2 infection

2021

Apart from prevention using vaccinations, the management options for COVID-19 remain limited. In retrospective cohort studies, use of famotidine, a specific oral H2 receptor antagonist (antihistamine), has been associated with reduced risk of intubation and death in patients hospitalized with COVID-19. In a case series, nonhospitalized patients with COVID-19 experienced rapid symptom resolution after taking famotidine, but the molecular basis of these observations remains elusive. Here we show using biochemical, cellular, and functional assays that famotidine has no effect on viral replication or viral protease activity. However, famotidine can affect histamine-induced signaling processes i…

EV-TRACK: transparent reporting and centralizing knowledge in extracellular vesicle research

2017

We argue that the field of extracellular vesicle (EV) biology needs more transparent reporting to facilitate interpretation and replication of experiments. To achieve this, we describe EV-TRACK, a crowdsourcing knowledgebase (http://evtrack.org) that centralizes EV biology and methodology with the goal of stimulating authors, reviewers, editors and funders to put experimental guidelines into practice.

CHK1-targeted therapy to deplete DNA replication-stressed, p53-deficient, hyperdiploid colorectal cancer stem cells.

2017

ObjectiveCancer stem cells (CSCs) are responsible for tumour formation and spreading, and their targeting is required for tumour eradication. There are limited therapeutic options for advanced colorectal cancer (CRC), particularly for tumours carrying RAS-activating mutations. The aim of this study was to identify novel CSC-targeting strategies.DesignTo discover potential therapeutics to be clinically investigated as single agent, we performed a screening with a panel of FDA-approved or investigational drugs on primary CRC cells enriched for CSCs (CRC-SCs) isolated from 27 patients. Candidate predictive biomarkers of efficacy were identified by integrating genomic, reverse-phase protein mic…

Lack of evidence of mimivirus replication in human PBMCs

2018

The Acanthamoeba polyphaga mimivirus (APMV) was first isolated during a pneumonia outbreak in Bradford, England, and since its discovery many research groups devoted efforts to understand whether this virus could be associated to human diseases, in particular clinical signs and symptoms of pneumonia. In 2013, we observed cytopathic effect in amoebas (rounding and lysis) inoculated with APMV inoculated PBMCs (peripheral blood mononuclear cell) extracts, and at that point we interpreted those results as mimivirus replication in human PBMCs. Based on these results we decided to further investigate APMV replication in human PBMCs, by transmission electron microscopy (TEM) and qPCR. No viral fac…

Constrained evolvability of interferon suppression in an RNA virus.

2016

AbstractInnate immunity responses controlled by interferon (IFN) are believed to constitute a major selective pressure shaping viral evolution. Viruses encode a variety of IFN suppressors, but these are often multifunctional proteins that also play essential roles in other steps of the viral infection cycle, possibly limiting their evolvability. Here, we experimentally evolved a vesicular stomatitis virus (VSV) mutant carrying a defect in the matrix protein (M∆51) that abolishes IFN suppression and that has been previously used in the context of oncolytic virotherapy. Serial transfers of this virus in normal, IFN-secreting cells led to a modest recovery of IFN blocking capacity and to weak …

ICTV Virus Taxonomy Profile: Solinviviridae

2019

Solinviviridae is a family of picorna/calici-like viruses with non-segmented, linear, positive-sense RNA genomes of approximately 10-11 kb. Unusually, their capsid proteins are encoded towards the 3'-end of the genome where they can be expressed both from a subgenomic RNA and as an extension of the replication (picorna-like helicase-protease-polymerase) polyprotein. Members of two species within the family infect ants, but related unclassified virus sequences derive from a large variety of insects and other arthropods. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the Solinviviridae, which is available at www.ictv.global/report/solinviviridae.

Antiviral Properties of Chemical Inhibitors of Cellular Anti-Apoptotic Bcl-2 Proteins

2017

Viral diseases remain serious threats to public health because of the shortage of effective means of control. To combat the surge of viral diseases, new treatments are urgently needed. Here we show that small-molecules, which inhibit cellular anti-apoptotic Bcl-2 proteins (Bcl-2i), induced the premature death of cells infected with different RNA or DNA viruses, whereas, at the same concentrations, no toxicity was observed in mock-infected cells. Moreover, these compounds limited viral replication and spread. Surprisingly, Bcl-2i also induced the premature apoptosis of cells transfected with viral RNA or plasmid DNA but not of mock-transfected cells. These results suggest that Bcl-2i sensiti…

Protoparvovirus Knocking at the Nuclear Door

2017

Protoparvoviruses target the nucleus due to their dependence on the cellular reproduction machinery during the replication and expression of their single-stranded DNA genome. In recent years, our understanding of the multistep process of the capsid nuclear import has improved, and led to the discovery of unique viral nuclear entry strategies. Preceded by endosomal transport, endosomal escape and microtubule-mediated movement to the vicinity of the nuclear envelope, the protoparvoviruses interact with the nuclear pore complexes. The capsids are transported actively across the nuclear pore complexes using nuclear import receptors. The nuclear import is sometimes accompanied by structural chan…

2019

Viruses frequently spread among cells or hosts in groups, with multiple viral genomes inside the same infectious unit. These collective infectious units can consist of multiple viral genomes inside the same virion, or multiple virions inside a larger structure such as a vesicle. Collective infectious units deliver multiple viral genomes to the same cell simultaneously, which can have important implications for viral pathogenesis, antiviral resistance, and social evolution. However, little is known about why some viruses transmit in collective infectious units, whereas others do not. We used a simple evolutionary approach to model the potential costs and benefits of transmitting in a collect…