Search results for "Replication"
showing 10 items of 489 documents
Cooperative nature of viral replication
2020
The ability of viruses to infect their hosts depends on rapid dissemination following transmission. The notion that viral particles function as independent propagules has been challenged by recent observations suggesting that viral aggregates show enhanced infectivity and faster spread. However, these observations remain poorly understood. Here, we show that viral replication is a cooperative process, such that entry of multiple viral genome copies into the same cell disproportionately increases short-term viral progeny production. This cooperativity arises from the positive feedback established between replication templates and virus-encoded products involved in replication and should be a…
IN SITU HYBRIDIZATION FOR DETECTION OF HEPATITIS B VIRUS GENOMES IN LIVER TISSUE OF CHRONIC INFECTED CHILDREN
1990
Detection of hepatitis B virus (HBV)-DNA in the liver of chronic infected patients is presently the most sensitive marker of viral replication and infectivity. In situ hybridization (ISH) allows the direct visualization of HBV infected liver cells and distribution of the viral sequences. This study was done to establish ISH and correlate the findings with conventional markers for HBV infection. Methods. Liver biopsies of 50 patients (28 ♂, 22 ♀) aged 0.5-20 years (mean 10.3) with various histological diagnoses were tested by 1SH. The HBV-DNA probe was labeled by nick translation with 35S-CTP to a specific activity of 3-5×108 cpm/μg DNA. Results. HBV-DNA/mRNA could be demonstrated in 38 pati…
Pathogenesis of HSV-1/2 induced vaginitis/vulvitis of the mouse: dependence of lesions on genetic properties of the virus and analysis of pathohistol…
1993
A scoring system for herpes simplex virus (HSV) induced vaginitis/vulvitis in Balb/c mice was delineated from vaginal infections. Four degrees of vaginitis/vulvitis could be distinguished after infection with suitable strains of HSV despite nearly identical replication rates. The time course of replication, inflammation and pathohistology was compared further. Grade 0 was defined by lack of symptoms despite presence of strong replication, which was detectable at days 3-6. Focal necrotic lesions of the epithelial layer were present containing HSV-specific antigens. DNA could be detected by hybridization only in the outer zone of these areas. At day 6 these zones began to be re-epithelialized…
The herpesviral antagonist m152 reveals differential activation of STING ‐dependent IRF and NF ‐κB signaling and STING 's dual role during MCMV infec…
2019
Cytomegaloviruses (CMVs) are master manipulators of the host immune response. Here, we reveal that the murine CMV (MCMV) protein m152 specifically targets the type I interferon (IFN) response by binding to stimulator of interferon genes (STING), thereby delaying its trafficking to the Golgi compartment from where STING initiates type I IFN signaling. Infection with an MCMV lacking m152 induced elevated type I IFN responses and this leads to reduced viral transcript levels both in vitro and in vivo This effect is ameliorated in the absence of STING Interestingly, while m152 inhibits STING-mediated IRF signaling, it did not affect STING-mediated NF-κB signaling. Analysis of how m152 targets S…
Cholesterol Dependence of Collagen and Echovirus 1 Trafficking along the Novel α2β1 Integrin Internalization Pathway
2013
We have previously shown that soluble collagen and a human pathogen, echovirus 1 (EV1) cluster α2β1 integrin on the plasma membrane and cause their internalization into cytoplasmic endosomes. Here we show that cholesterol plays a major role not only in the uptake of α2β1 integrin and its ligands but also in the formation of α2 integrin-specific multivesicular bodies (α2-MVBs) and virus infection. EV1 infection and α2β1 integrin internalization were totally halted by low amounts of the cholesterol-aggregating drugs filipin or nystatin. Inhibition of cholesterol synthesis and accumulation of lanosterol after ketoconazole treatment inhibited uptake of collagen, virus and clustered integrin, an…
Internalization of Echovirus 1 in Caveolae
2002
ABSTRACT Echovirus 1 (EV1) is a human pathogen which belongs to the Picornaviridae family of RNA viruses. We have analyzed the early events of infection after EV1 binding to its receptor α2β1 integrin and elucidated the route by which EV1 gains access to the host cell. EV1 binding onto the cell surface and subsequent entry resulted in conformational changes of the viral capsid as demonstrated by sucrose gradient sedimentation analysis. After 15 min to 2 h postinfection (p.i.) EV1 capsid proteins were seen in vesicular structures that were negative for markers of the clathrin-dependent endocytic pathway. In contrast, immunofluorescence confocal microscopy showed that EV1, α2β1 integrin, and …
The elemental role of iron in DNA synthesis and repair
2017
Iron is an essential redox element that functions as a cofactor in many metabolic pathways. Critical enzymes in DNA metabolism, including multiple DNA repair enzymes (helicases, nucleases, glycosylases, demethylases) and ribonucleotide reductase, use iron as an indispensable cofactor to function. Recent striking results have revealed that the catalytic subunit of DNA polymerases also contains conserved cysteine-rich motifs that bind iron–sulfur (Fe/S) clusters that are essential for the formation of stable and active complexes. In line with this, mitochondrial and cytoplasmic defects in Fe/S cluster biogenesis and insertion into the nuclear iron-requiring enzymes involved in DNA synthesis a…
Digital innovation & enterprise in the sharing economy: An action research agenda
2020
Abstract In this digital era, Digital Innovation & Enterprise have emerged as a possible prescription in the sharing economy. Scholars have noted that digital innovation is transforming the technological landscape, entrepreneurial practices, and the behaviours, attitudes, and beliefs of consumers across the globe. This research note serves three purposes. First, it introduces digital innovation and enterprise as a fruitful area of research in the sharing economy. Second, it extends the agenda set by Yoo, Henfridsson, and Lyytinen (2010) on “new organising logics of Digital Innovation” to propose contemporary research questions for scholarly collaboration. Third, it attempts to move forward …
Introducing SD modelling into planning and control systems to manage SMEs' growth: a learning-oriented perspective
2002
This article emphasises the need for a learning-oriented approach to planning and control as a prerequisite for SMEs’ survival and growth. Such a perspective can be effectively pursued through the development of interactive learning environments linking system dynamics (SD) and accounting models, which provide two complementary views of business phenomena. In order to properly support the drawing up of business plans and the evaluation of results associated with their implementation, the use of financial SD models embodying the accounting perspective is recommended. This is likely to enhance a shift in SME key actors’ minds, as they will be able to analyse under the feedback view financial …
Pragmatic markers resulting from language contact. The case of sañani in Aymara
2020
This paper explores the pragmatic functions of a previously unattested pragmatic marker (Fraser, 1996, 2006) found in Aymara, i.e. sanani ‘let’s say’. The uses of sanani suggest that this marker is the result of the influence of Spanish on Aymara due to sustained language contact. Sanani seems to be the “replication” (Heine and Kuteva, 2005) of the Spanish pragmatic marker digamos ‘let’s say’. Like digamos (Grande Alija, 2010; Quartararo, 2017a), sanani functions as a pragmatic marker by signaling either an inferential process or the semantic relation between two discourse segments. The original data used for this analysis was gathered through the Family Problems Picture task (San Roque et …