2-Deoxy-D-glucose inhibits lymphocytic choriomeningitis virus propagation by targeting glycoprotein N-glycosylation.

Background: Increased glucose uptake and utilization via aerobic glycolysis are among the most prominent hallmarks of tumor cell metabolism. Accumulating evidence suggests that similar metabolic changes are also triggered in many virus-infected cells. Viral propagation, like highly proliferative tumor cells, increases the demand for energy and macromolecular synthesis, leading to high bioenergetic and biosynthetic requirements.

Cellular Lipids-Hijacked Victims of Viruses.

Over the millions of years-long co-evolution with their hosts, viruses have evolved plenty of mechanisms through which they are able to escape cellular anti-viral defenses and utilize cellular pathways and organelles for replication and production of infectious virions. In recent years, it has become clear that lipids play an important role during viral replication. Viruses use cellular lipids in a variety of ways throughout their life cycle.

Metabolic reprogramming as a feast for virus replication.

Viral replication depends entirely on the energy and biosynthetic precursors supplied by the host cell metabolic network. Viruses actively reprogram host cell metabolism to establish optimal environment for their replication and spread. They stimulate the uptake of extracellular nutrients and predominantly modulate glucose, glutamine, and fatty acid metabolism to support anabolic metabolic pathways.

Quantitative Proteomics Reveal Peroxiredoxin Perturbation Upon Persistent Lymphocytic Choriomeningitis Virus Infection in Human Cells.

Experimental data indicate that during persistent infection, lymphocytic choriomeningitis virus (LCMV) may both directly or indirectly modulate regulatory cellular processes and alter cellular functions that are not critical for survival, but are essential for cell homeostasis. In order to shed more light on these processes, two-dimensional differential in-gel electrophoresis (2D-DIGE) and MALDI-TOF tandem mass spectrometry were used to determine the proteome response of the HeLa cell line to persistent LCMV infection. Quantitative analysis revealed 24 differentially abundant proteins.

Pyruvate dehydrogenase kinase 1 and carbonic anhydrase IX targeting in hypoxic tumors.

Pyruvate dehydrogenase kinase 1 (PDHK1) and carbonic anhydrase IX (CAIX) are some of the most hypoxia-inducible proteins associated with tumors, implicated in glucose metabolism and pH regulation, respectively. They both appear to be necessary for model tumor growth, and their high level of expression in human tumors predicts poor patient outcome. Another thing they have in common is that hypoxia not only induces their expression but also their enzymatic activity.

Chronic low-dose pro-oxidant treatment stimulates transcriptional activity of telomeric retroelements and increases telomere length in Drosophila.

It has been proposed that oxidative stress, elicited by high levels of reactive oxygen species, accelerates telomere shortening by erosion of telomeric DNA repeats. While most eukaryotes counteract telomere shortening by telomerase-driven addition of these repeats, telomeric loss in Drosophila is compensated by retrotransposition of the telomeric retroelements HeT-A, TART and TAHRE to chromosome ends. In this study we tested the effect of chronic exposure of flies to non-/sub-lethal doses of paraquat, which is a redox cycling compound widely used to induce oxidative stress in various experimental paradigms including telomere length analyses.

A simple method for isolation of cell-associated viral particles from cell culture.

A common method for cell-associated virus isolation involves disruption of infected cells by a combination of hypotonic burst, freeze-thaw cycles (F-T) and sonication. This protocol was also originally used for the preparation of cell-free extract containing the MX strain of lymphocytic choriomeningitis virus (LCMV), which is preferentially propagated by cell-to-cell contact and does not release distinct virions into the medium. In the present study, we compared different approaches to virus isolation.

Development and application of ELISA for the detection of IgG antibodies to lymphocytic choriomeningitis virus.

Lymphocytic choriomeningitis virus (LCMV) is a neglected human pathogen, which can cause severe illnesses in humans. The most vulnerable are the human foetus and immunosuppressed individuals. Since there is no commercially available enzyme-linked immunosorbent assay (ELISA) for the diagnosis of anti-LCMV antibodies in human sera, we developed a sandwich ELISA method detecting anti-nucleoprotein IgG antibodies, using a specific monoclonal anti-nucleoprotein antibody and cells persistently infected with LCMV strain MX as antigen.

Antiviral Effect of Interferon Lambda Against Lymphocytic Choriomeningitis Virus.

Lambda interferons inhibit replication of many viruses, but their role in the inhibition of lymphocytic choriomeningitis virus (LCMV) infection remains unclear. In this study, we examined the antiviral effects of interferon (IFN)-λ2 and IFN-λ3 against LCMV in A549 cells. We found that IFN-λ2 is a more potent inhibitor of LCMV strain MX compared with IFN-λ3, whereas both cytokines have similar antiviral effects against an immunosuppressive variant of LCMV, clone-13.

Interferons lambda, new cytokines with antiviral activity.

Interferons (IFNs) are key cytokines in the establishment of a multifaceted antiviral response. Three distinct types of IFNs are now recognized (type I, type II, and type III) based on their receptor usage, structural features and biological activities. Although all IFNs are important mediators of antiviral protection, their roles in antiviral defence vary.

Lymphocytic choriomeningitis virus: invisible but not innocent.

Lymphocytic choriomeningitis virus (LCMV) attracts significant attention both as an important experimental model system to study acute and persistent viral infections, and as a neglected human pathogen of clinical significance. This review focuses on the basic aspects and recent advances in the molecular and cell biology of LCMV, the outcome of LCMV infection on its natural host with an emphasis on persistent infection and the outcome of LCMV infection in humans. Lastly, we summarize our contribution to current knowledge on LCM virus.

Hypoxia induces the gene expression and extracellular transmission of persistent lymphocytic choriomeningitis virus.

The physiological context of virus-infected cells can markedly affect multiplication and spread of the virus progeny. During persistent infection, the virus exploits the host cell without disturbing its vital functions. However, microenvironmental hypoxia can uncouple this intimate relationship and escalate virus pathogenesis.

The nucleoprotein of lymphocytic choriomeningitis virus facilitates spread of persistent infection through stabilization of the keratin network.

Lymphocytic choriomeningitis virus (LCMV) is a prototypic arenavirus containing a bisegmented single-stranded RNA genome with an ambisense coding strategy. MX is a noncytolytic LCMV strain with an in vitro host range restricted to only few cell lines. MX LCMV spreads via cell-cell contacts and causes persistent infection with high production of viral nucleoprotein (NP).

Type 2 IP(3) receptors are involved in uranyl acetate induced apoptosis in HEK 293 cells.

Calcium released from endoplasmic reticulum through special calcium release channels - inositol 1,4,5-trisphosphate receptors (IP(3)Rs) and ryanodine receptors (RyRs) - serves as a main source of cytosolic calcium signaling in the majority of cell types in physiological state and also in pathological situations. In this work, we studied whether IP(3)Rs can be involved in uranyl acetate induced nephrotoxicity. Using human embryonic kidney cell line (HEK293) as an experimental model we have found that uranyl acetate (5 and 50microM) up-regulates both, mRNA and protein levels of the type 1 and type 2 IP(3) receptors in HEK293 cells.

Molecular characterization of the genes coding for glycoprotein and L protein of lymphocytic choriomeningitis virus strain MX.

Lymphocytic choriomeningitis virus (LCMV) is the prototype Arenavirus with ambisense coding strategy. We have previously described a new MX strain LCMV and determined the primary structure of the genes coding for the nucleoprotein and RING finger Z protein. In this report, we describe amplification and sequencing of the entire coding sequences of additional MX genes, the glycoprotein precursor (GPC) and L protein.

Up-regulation of Murid herpesvirus 4 ORF50 by hypoxia: possible implication for virus reactivation from latency.

Murid herpesvirus 4 (MuHV-4) is a member of the Gammaherpesvirus subfamily capable to establish a long-lasting latency and induce occasional malignancies. Because MuHV-4 is associated with cancer in a subset of virus-infected mice and because tumor development is often linked with hypoxia, we studied the influence of hypoxia on the biology of this virus. Using immunofluorescence and FACS analysis we detected increased proportion of MuHV-4 positive cells in the latently infected NB-78 cell line exposed to low oxygen conditions compared to normoxic controls.

Sequence analysis of the regions flanking terminal repeats of the genome of umava isolate of murine gammaherpesvirus.

The umava isolate of murine gammaherpesvirus (MHV-umava) slightly differs from Murine gammaherpesvirus 68 (MHV-68) and two other isolates of murine gammaherpesvirus (MHV), MHV-76 and MHV-72 in some biological properties. To identify the region(s) in the MHV-umava genome responsible for this phenomenon, we compared the sequences flanking terminal repeats (TRs) of the MHV-umava genome with those of MHV-68, MHV-76 and MHV-72. Restriction and sequence analyses revealed in MHV-umava as compared to MHV-68 approximately 9.

Inhibitory effect of DIDS, NPPB, and phloretin on intracellular chloride channels.

We studied the effects of the chloride channel blockers, 5-nitro-2-(phenylpropylamino)-benzoate (NPPB), dihydro-4,4' diisothiocyanostilbene-2,2'-disulphonic acid (DIDS), and phloretin on H2O2-induced primary culture cardiomyocyte apoptosis and activity of intracellular chloride channels obtained from rat heart mitochondrial and lysosomal vesicles. The chloride channel blockers (100 micromol/l) inhibited the H2O2-induced cardiomyocytes apoptosis. We characterized the effect of the blockers on single channel properties of the chloride channels derived from the mitochondrial and lysosomal vesicles incorporated into a bilayer lipid membrane.

Lymphocytic choriomeningitis virus mx strain does not induce the expression of tumor-associated carbonic anhydrase IX in persistently infected HeLa cells.

Summary. - Lymphocytic choriomeningitis virus (LCMV) is an arenavirus that readily causes persistent infections, in which it does not interfere with vital functions of the cells, but can affect expression of "luxurious" genes. MX strain of LCMV (MX LCMV) has been identified as an agent transmissible by cell-to-cell contact in the human carcinoma MaTu cells grown in a mixed culture with HeLa cells.

A polymorphic monoclonal anti-BoLA class I antibody.

Cytotoxic monoclonal antibody IVA 44 was generated after the intraperitoneal immunization with peripheral blood mononuclear (PBM) cells and the boost by the intrasplenic inoculation of skin graft. The detected membrane antigen isolated by immunoprecipitation appears to be composed of two subunits characteristic for the MHC class I molecules. The antibody IVA 44 exhibited a different reactivity: it recognized the BoLA A14 (A8) specificity in animals typed in the Fifth BoLA workshop, while it reacted with all A8 positive animals including subtypes A14 and A15 in Czech and Slovak cattle.