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showing 10 items of 31271 documents
Baculovirus-mediated immediate-early gene expression and nuclear reorganization in human cells
2007
Baculovirus, Autographa californica multiple nucleopolyhedrovirus (AcMNPV), has the ability to transduce mammalian cell lines without replication. The general objective of this study was to detect the transcription and expression of viral immediate-early genes in human cells and to examine the interactions between viral components and subnuclear structures. Viral capsids were seen in large, discrete foci in nuclei of both dividing and non-dividing human cells. Concurrently, the transcription of viral immediate-early transregulator genes (ie-1, ie-2) and translation of IE-2 protein were detected. Quantitative microscopy imaging and analysis showed that virus transduction altered the size of …
Impact of VP1-Specific Protein Sequence Motifs on Adeno-Associated Virus Type 2 Intracellular Trafficking and Nuclear Entry
2012
ABSTRACT Adeno-associated virus type 2 (AAV2) has gained much interest as a gene delivery vector. A hallmark of AAV2-mediated gene transfer is an intracellular conformational change of the virus capsid, leading to the exposure of infection-relevant protein domains. These protein domains, which are located on the N-terminal portion of the structural proteins VP1 and VP2, include a catalytic phospholipase A 2 domain and three clusters of basic amino acids. We have identified additional protein sequence motifs located on the VP1/2 N terminus that also proved to be obligatory for virus infectivity. These motifs include signals that are known to be involved in protein interaction, endosomal sort…
In vitro studies on the activation of the hepatitis C virus NS3 proteinase by the NS4A cofactor.
1996
AbstractProteolytic processing of the nonstructural proteins of the hepatitis C virus (HCV) is mediated by two viral proteinases: the NS2-3 proteinase cleaving at the NS2/3 junction and the NS3 serine-type proteinase responsible for processing at the NS3/4A, NS4A/B, NS4B/5A, and NS5A/B sites. Activity of the NS3 proteinase is modulated by NS4A. In the absence of this cofactor processing at the NS3-dependent sites does not occur or, in the case of the NS5A/B junction, is poor but increased when NS4A is present. Although recent studies demonstrated that proteinase activation requires direct interaction between NS3 and NS4A, the mechanism by which NS4A exerts the activation function is not kno…
Single amino acid substitutions in the glycoprotein B carboxy terminus influence the fusion from without property of herpes simplex virus type 1.
1995
Syncytial mutations of herpes simplex virus type 1 (HSV-1) strains ANG, ANG path, HFEM, tsB5 and HSZP cause extensive cell fusion and were mapped to the cytoplasmic domain of glycoprotein B (gB), within the syn 3 locus. These strains are so far the only ones which show the phenotype ‘fusion from without’ (FFWO): 60 min after infection with high m.o.i., cells in a tissue culture are fused without transcription and translation of the viral genome. In this report we detected, using the recombinants 27/III and K-7, that an amino acid exchange from Ala to Val at aa position 854 of gB is the main determinant for FFWO activity of strains ANG, ANG path and recombinant K-7. The transfer of this muta…
Oncolytic targeting of renal cell carcinoma via encephalomyocarditis virus
2010
Apoptosis is a fundamental host defence mechanism against invading microbes. Inactivation of NF-kappaB attenuates encephalomyocarditis virus (EMCV) virulence by triggering rapid apoptosis of infected cells, thereby pre-emptively limiting viral replication. Recent evidence has shown that hypoxia-inducible factor (HIF) increases NF-kappaB-mediated anti-apoptotic response in clear-cell renal cell carcinoma (CCRCC) that commonly exhibit hyperactivation of HIF due to the loss of its principal negative regulator, von Hippel-Lindau (VHL) tumour suppressor protein. Here, we show that EMCV challenge induces a strong NF-kappaB-dependent gene expression profile concomitant with a lack of interferon-me…
Clathrin- and Caveolin-Independent Entry of Human Papillomavirus Type 16—Involvement of Tetraspanin-Enriched Microdomains (TEMs)
2008
BACKGROUND: Infectious entry of human papillomaviruses into their host cells is an important step in the viral life cycle. For cell binding these viruses use proteoglycans as initial attachment sites. Subsequent transfer to a secondary receptor molecule seems to be involved in virus uptake. Depending on the papillomavirus subtype, it has been reported that entry occurs by clathrin- or caveolin-mediated mechanisms. Regarding human papillomavirus type 16 (HPV16), the primary etiologic agent for development of cervical cancer, clathrin-mediated endocytosis was described as infectious entry pathway. METHODOLOGY/PRINCIPAL FINDINGS: Using immunofluorescence and infection studies we show in contra…
Quantitative microscopy reveals stepwise alteration of chromatin structure during herpesvirus infection
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…
Tumor targeting of baculovirus displaying a lymphatic homing peptide.
2008
Background Tumor-associated cells and vasculature express attractive molecular markers for site-specific vector targeting. To attain tumor-selective tropism, we recently developed a baculovirus vector displaying the lymphatic homing peptide LyP-1, originally identified by ex vivo/in vivo screening of phage display libraries, on the viral envelope by fusion to the transmembrane anchor of vesicular stomatitis virus G-protein. Methods In the present study, we explored the specificity and kinetics of viral binding and internalization as well as in vivo tumor homing of the LyP-1 displaying virus to elucidate the applicability of baculovirus for targeted therapies. Results We demonstrated that th…
Game-Theoretic Approach to Hölder Regularity for PDEs Involving Eigenvalues of the Hessian
2021
AbstractWe prove a local Hölder estimate for any exponent $0<\delta <\frac {1}{2}$ 0 < δ < 1 2 for solutions of the dynamic programming principle $$ \begin{array}{@{}rcl@{}} u^{\varepsilon} (x) = \sum\limits_{j=1}^{n} \alpha_{j} \underset{\dim(S)=j}{\inf} \underset{|v|=1}{\underset{v\in S}{\sup}} \frac{u^{\varepsilon} (x + \varepsilon v) + u^{\varepsilon} (x - \varepsilon v)}{2} \end{array} $$ u ε ( x ) = ∑ j = 1 n α j inf dim ( S ) = j sup v ∈ S | v | = 1 u ε ( x + ε v ) + u ε ( x − ε v ) 2 with α1,αn > 0 and α2,⋯ ,αn− 1 ≥ 0. The proof is based on a new coupling idea from game theory. As an application, we get the same regularity estimate for viscosity solutions of the PDE $…
Regularity for nonlinear stochastic games
2015
We establish regularity for functions satisfying a dynamic programming equation, which may arise for example from stochastic games or discretization schemes. Our results can also be utilized in obtaining regularity and existence results for the corresponding partial differential equations. peerReviewed