Search results for "Replica"
showing 10 items of 576 documents
Murine model of interstitial cytomegalovirus pneumonia in syngeneic bone marrow transplantation: persistence of protective pulmonary CD8-T-cell infil…
2000
ABSTRACTInterstitial pneumonia (IP) is a severe organ manifestation of cytomegalovirus (CMV) disease in the immunocompromised host, in particular in recipients of bone marrow transplantation (BMT). Diagnostic criteria for the definition of CMV-IP include clinical evidence of pneumonia together with CMV detected in bronchoalveolar lavage or lung biopsy. We have used the model of syngeneic BMT and simultaneous infection of BALB/c mice with murine CMV for studying the pathogenesis of CMV-IP by controlled longitudinal analysis. A disseminated cytopathic infection of the lungs with fatal outcome was observed only when reconstituting CD8 T cells were depleted. Neither CD8 nor CD4 T cells mediated…
Persistent and Transient Replication of Full-Length Hepatitis C Virus Genomes in Cell Culture
2002
ABSTRACT The recently developed subgenomic hepatitis C virus (HCV) replicons were limited by the fact that the sequence encoding the structural proteins was missing. Therefore, important information about a possible influence of these proteins on replication and pathogenesis and about the mechanism of virus formation could not be obtained. Taking advantage of three cell culture-adaptive mutations that enhance RNA replication synergistically, we generated selectable full-length HCV genomes that amplify to high levels in the human hepatoma cell line Huh-7 and can be stably propagated for more than 6 months. The structural proteins are efficiently expressed, with the viral glycoproteins E1 and…
Pricing and hedging GDP-linked bonds in incomplete markets
2018
Abstract We model the super-replication of payoffs linked to a country’s GDP as a stochastic linear program on a discrete time and state-space scenario tree to price GDP-linked bonds. As a byproduct of the model we obtain a hedging portfolio. Using linear programming duality we compute also the risk premium. The model applies to coupon-indexed and principal-indexed bonds, and allows the analysis of bonds with different design parameters (coupon, target GDP growth rate, and maturity). We calibrate for UK and US instruments, and carry out sensitivity analysis of prices and risk premia to the risk factors and bond design parameters. We also compare coupon-indexed and principal-indexed bonds. F…
Pricing and Hedging GDP-Linked Bonds in Incomplete Markets
2017
We model the super-replication of payoffs linked to a country's GDP as a stochastic linear program on a discrete time and state-space scenario tree to price GDP-linked bonds. As a byproduct of the model, we obtain a hedging portfolio. Using linear programming duality we also compute the risk premium. The model applies to coupon-indexed and principal-indexed bonds, and allows the analysis of bonds with different design parameters (coupon, target GDP growth rate, and maturity). We calibrate for UK and US instruments and carry out a sensitivity analysis of prices and risk premia to the risk factors and bond design parameters. We also compare coupon-indexed and principal-indexed bonds. Results …
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 …