Search results for "virology."

Mechanisms of viral mutation

2016

The remarkable capacity of some viruses to adapt to new hosts and environments is highly dependent on their ability to generate de novo diversity in a short period of time. Rates of spontaneous mutation vary amply among viruses. RNA viruses mutate faster than DNA viruses, single-stranded viruses mutate faster than double-strand virus, and genome size appears to correlate negatively with mutation rate. Viral mutation rates are modulated at different levels, including polymerase fidelity, sequence context, template secondary structure, cellular microenvironment, replication mechanisms, proofreading, and access to post-replicative repair. Additionally, massive numbers of mutations can be intro…

Human norovirus hyper-mutation revealed by ultra-deep sequencing

2016

Human noroviruses (NoVs) are a major cause of gastroenteritis worldwide. It is thought that, similar to other RNA viruses, high mutation rates allow NoVs to evolve fast and to undergo rapid immune escape at the population level. However, the rate and spectrum of spontaneous mutations of human NoVs have not been quantified previously. Here, we analyzed the intra-patient diversity of the NoV capsid by carrying out RT-PCR and ultra-deep sequencing with 100,000-fold coverage of 16 stool samples from symptomatic patients. This revealed the presence of low-frequency sequences carrying large numbers of U-to-C or A-to-G base transitions, suggesting a role for hyper-mutation in NoV diversity. To mor…

High Fidelity Deep Sequencing Reveals No Effect of ATM, ATR, and DNA-PK Cellular DNA Damage Response Pathways on Adenovirus Mutation Rate

2019

This article belongs to the Section Animal Viruses.

Difference in Markers of Microbial Translocation and Cell Apoptosis in HIV Monoinfected and HIV/HCV Coinfected Patients

2019

Abstract Immune activation in human immunodeficiency virus (HIV) infection is driven by microbial translocation and in HIV patients is one of the contributors to faster progression of liver disease along with increased cell apoptosis. The aim of the study was to compare microbial translocation and apoptosis markers in HIV monoinfected and HIV/hepatitis C virus (HCV) coinfected patients, depending on HIV immune status and antiretroviral treatment (ART). We analysed data for 78 HIV monoinfected and 105 HIV/HCV coinfected patients from the Rīga East University Hospital. Lipopolysaccharide (LPS), endotoxin core antibodies (EndoCAb), cytokeratin 18 (CK18) and cyto-chrome c (Cyt-c) levels were me…

2019

During lytic herpes simplex virus 1 (HSV-1) infection, the expansion of the viral replication compartments leads to an enrichment of the host chromatin in the peripheral nucleoplasm. We have shown previously that HSV-1 infection induces the formation of channels through the compacted peripheral chromatin. Here, we used three-dimensional confocal and expansion microscopy, soft X-ray tomography, electron microscopy, and random walk simulations to analyze the kinetics of host chromatin redistribution and capsid localization relative to their egress site at the nuclear envelope. Our data demonstrated a gradual increase in chromatin marginalization, and the kinetics of chromatin smoothening arou…

Large Blooms of Bacillales (Firmicutes) Underlie the Response to Wetting of Cyanobacterial Biocrusts at Various Stages of Maturity.

2018

ABSTRACT Biological soil crusts (biocrusts) account for a substantial portion of primary production in dryland ecosystems. They successionally mature to deliver a suite of ecosystem services, such as carbon sequestration, water retention and nutrient cycling, and climate regulation. Biocrust assemblages are extremely well adapted to survive desiccation and to rapidly take advantage of the periodic precipitation events typical of arid ecosystems. Here we focus on the wetting response of incipient cyanobacterial crusts as they mature from “light” to “dark.” We sampled a cyanobacterial biocrust chronosequence before (dry) and temporally following a controlled wetting event and used high-throug…

Pre-ART HIV-1 DNA in CD4+ T cells correlates with baseline viro-immunological status and outcome in patients under first-line ART

2018

Objectives We evaluated the association between pre-ART HIV DNA and HIV-infected participant characteristics at baseline as well as with their response to first-line ART. Methods Four hundred and thirty-three patients from the ICONA cohort, starting first-line ART after the year 2000, were analysed. Pre-ART HIV DNA was quantified with the modified COBAS TaqMan HIV-1 Test and normalized by CD4+ T cells. Linear correlation between pre-ART HIV DNA and other continuous markers (HIV RNA, CD4 count, markers of inflammation and coagulation) at baseline was evaluated by means of Pearson correlation coefficient and a linear regression model. Survival analyses and Cox regression models were used to s…

Recommendations for the introduction of metagenomic high-throughput sequencing in clinical virology, part I: Wet lab procedure

2020

Metagenomic high-throughput sequencing (mHTS) is a hypothesis-free, universal pathogen detection technique for determination of the DNA/RNA sequences in a variety of sample types and infectious syndromes. mHTS is still in its early stages of translating into clinical application. To support the development, implementation and standardization of mHTS procedures for virus diagnostics, the European Society for Clinical Virology (ESCV) Network on Next-Generation Sequencing (ENNGS) has been established. The aim of ENNGS is to bring together professionals involved in mHTS for viral diagnostics to share methodologies and experiences, and to develop application recommendations. This manuscript aims…

Characterization of a Novel Conformational GII.4 Norovirus Epitope: Implications for Norovirus-Host Interactions

2016

ABSTRACT Human noroviruses (NoVs) are the main etiological agents of acute gastroenteritis worldwide. While NoVs are highly diverse (more than 30 genotypes have been detected in humans), during the last 40 years most outbreaks and epidemics have been caused by GII.4 genotype strains, raising questions about their persistence in the population. Among other potential explanations, immune evasion is considered to be a main driver of their success. In order to study antibody recognition and evasion in detail, we analyzed a conformational epitope recognized by a monoclonal antibody (3C3G3) by phage display, site-directed mutagenesis, and surface plasmon resonance. Our results show that the predi…

2019

Abstract Type B Coxsackieviruses (CVBs) are a common cause of acute and chronic myocarditis, dilated cardiomyopathy and aseptic meningitis. However, no CVB-vaccines are available for human use. We have previously produced virus-like particles (VLPs) for CVB3 with a baculovirus-insect cell production system. Here we have explored the potential of a VLP-based vaccine targeting CVB1 and describe the production of CVB1-VLPs with a scalable VLP purification method. The developed purification method consisting of tangential flow filtration and ion exchange chromatography is compatible with industrial scale production. CVB1-VLP vaccine was treated with UV-C or formalin to study whether stability a…