Glycosaminoglycan-binding microbial proteins in tissue adhesion and invasion: key events in microbial pathogenicity. (9/2188)

Glycosaminoglycans such as heparin, heparan sulphate and dermatan sulphate, are distributed widely in the human body. Several glycosaminoglycans form part of the extracellular matrix and heparan sulphate is expressed on all eukaryotic surfaces. The identification of specific binding to different glycosaminoglycan molecules by bacteria (e.g., Helicobacter pylori, Bordetella pertussis and Chlamydia trachomatis), viruses (e.g., herpes simplex and dengue virus), and protozoa (e.g., Plasmodium and Leishmania), is therefore of great interest. Expression of glycosaminoglycan-binding proteins depends on growth and culture conditions in bacteria, and differs in various phases of parasite development. Glycosaminoglycan-binding microbial proteins may mediate adhesion of microbes to eukaryotic cells, which may be a primary mechanism in mucosal infections, and are also involved in secondary effects such as adhesion to cerebral endothelia in cerebral malaria or to synovial membranes in arthritis caused by Borrelia burgdorferi. It has been suggested that they may enhance intracellular survival in macrophages. Microbial binding of heparin may interfere with heparin-dependent growth factors. Whether or not glycosaminoglycan-binding proteins mediate invasion of epithelial cells is a matter of controversy. Heparin and other glycosaminoglycans may have potential uses as therapeutic agents in microbial infections and could form part of future vaccines against such infections.  (+info)

Investigation of cell culture media infected with viruses by pyrolysis mass spectrometry: implications for bioaerosol detection. (10/2188)

Mass spectrometry coupled with a pyrolysis inlet system was used to investigate media from cell cultures infected with viruses. Cell culture media is an intricate mixture of numerous chemical constituents and cells that collectively produce complicated mass spectra. Cholesterol and free fatty acids were identified and attributed to lipid sources in the media (blood serum supplement and plasma membranes of host cells). These lipid moieties could be utilized as signature markers for rapidly detecting the cell culture media. Viruses are intracellular parasites and are dependent upon host cells in order to exist. Therefore, it is highly probable that significant quantities of media needed to grow and maintain viable host cells would be present if a viral agent were disseminated as an aerosol into the environment. Cholesterol was also detected from a purified virus sample, further substantiating its use as a target compound for detection. Implications of this research for detection of viral bioaerosols, using a field-portable pyrolysis mass spectrometer, is described.  (+info)

New substrates of DNA polymerases. (11/2188)

Bis-(2'-deoxynucleoside) 5',5'-tetraphosphates and bis-(2'-deoxynucleoside) 5',5'-triphosphates were shown to be a new type of substrate for several DNA polymerases of human, bacterial and viral origin. Their substrate properties depend both on their structure and on the nature of the enzyme. They are incorporated by both termini in correspondence with the template nucleotide program in the active center. The results obtained support the mechanism of their direct incorporation rather than prior hydrolysis to dNTP. The highest activity of these compounds was observed for HIV reverse transcriptase. The probable biological significance of the reaction is discussed.  (+info)

Evolution and horizontal transfer of dUTPase-encoding genes in viruses and their hosts. (12/2188)

dUTPase is a ubiquitous and essential enzyme responsible for regulating cellular levels of dUTP. The dut gene exists as single, tandemly duplicated, and tandemly triplicated copies. Crystallized single-copy dUTPases have been shown to assemble as homotrimers. dUTPase is encoded as an auxiliary gene in a number of virus genomes. The origin of viral dut genes has remained unresolved since their initial discovery. A comprehensive analysis of dUTPase amino acid sequence relationships was performed to explore the evolutionary dynamics of dut in viruses and their hosts. Our data set, comprised of 24 host and 51 viral sequences, includes representative sequences from available eukaryotes, archaea, eubacteria cells, and viruses, including herpesviruses. These amino acid sequences were aligned by using a hidden Markov model approach developed to align divergent data. Known secondary structures from single-copy crystals were mapped onto the aligned duplicate and triplicate sequences. We show how duplicated dUTPases might fold into a monomer, and we hypothesize that triplicated dUTPases also assemble as monomers. Phylogenetic analysis revealed at least five viral dUTPase sequence lineages in well-supported monophyletic clusters with eukaryotic, eubacterial, and archaeal hosts. We have identified all five as strong examples of horizontal transfer as well as additional potential transfer of dut genes among eubacteria, between eubacteria and viruses, and between retroviruses. The evidence for horizontal transfers is particularly interesting since eukaryotic dut genes have introns, while DNA virus dut genes do not. This implies that an intermediary retroid agent facilitated the horizontal transfer process between host mRNA and DNA viruses.  (+info)

Case-control study of non-Hodgkin's lymphoma among women and heterosexual men in the San Francisco Bay Area, California. (13/2188)

A population-based case-control study was conducted between 1988 and 1995 in the San Francisco Bay Area of California to determine risk factors for non-Hodgkin's lymphoma. Participants completed in-person interviews, and blood was drawn to test for viruses and lymphocyte subsets. This report includes data for 1,281 cases and 2,095 controls. In multivariate analyses, the factors associated with a decreased risk for non-Hodgkin's lymphoma were allergy to plants, bee and wasp stings, five or more vaccinations, drugs to lower blood cholesterol, nonsteroidal anti-inflammatory drugs, total number of sexual partners, and lifetime marijuana use, whereas an increased risk was associated with cimetidine and other histamine H2-receptor antagonists, splenectomy, gonorrhea, and body mass index. Unique to sex-specific models was an increased risk for endocrine gland disorders among women and for polio among men. Median CD3, CD4, CD8, CD20, and lymphocyte counts for non-Hodgkin's lymphoma patients were significantly lower than those for controls. These results implicate environmental factors that may influence the early stages of lymphomagenesis by stimulating the immune system. Antigen-driven B cells that accumulate to form lymphoma may be suppressed by immunologic stresses such as exposure to an increased number of sexual partners and to certain medications. A history of allergies provides evidence for a persistent capacity for B-cell differentiation and therefore a decreased accumulation of B cells. The decreased risk for non-Hodgkin's lymphoma with use of nonsteroidal anti-inflammatory drugs and cholesterol-lowering drugs is consistent with a macrophage inflammatory role in B-cell proliferation.  (+info)

Multimodal cancer treatment mediated by a replicating oncolytic virus that delivers the oxazaphosphorine/rat cytochrome P450 2B1 and ganciclovir/herpes simplex virus thymidine kinase gene therapies. (14/2188)

Multimodal therapy is generally more effective than single-agent treatment for cancer. rRp450 is an engineered herpes simplex viral mutant that replicates in and kills tumor cells in a relatively selective fashion. It also expresses, in infected cells, the cyclophosphamide (CPA)-sensitive rat cytochrome P450 2B1 (CYP2B1) and the ganciclovir (GCV)-sensitive herpes simplex virus thymidine kinase (HSV-TK) transgenes. We show that cultured rat 9L and human U87deltaEGFR glioma cells, infected and lysed by rRp450, also exhibit supra-additive sensitivity to both CPA and GCV, as determined by Chou-Talalay synergy analysis. DNA cross-linking, assayed by ethidium bromide fluorescence, was significantly inhibited in the presence of GCV, suggesting that interactions between the CPA/CYP2B1 and GCV/HSV-TK gene therapies occurred at the level of DNA repair. In vivo, regression of 9L s.c. tumor volumes in athymic mice was achieved only by the multimodal treatment allowed by rRp450 viral oncolysis combined with CPA/CYP2B1 and GCV/HSV-TK gene therapies, whereas all other treatment combinations produced only tumor growth retardation.  (+info)

Validity of fecal coliforms, total coliforms, and fecal streptococci as indicators of viruses in chlorinated primary sewage effluents. (15/2188)

Quantities of combined chlorine that usually destroyed more than 99.999% of the indigenous fecal coliforms, total coliforms, and fecal streptococci in primary sewage effluents destroyed only 85 to 99% of the indigenous viruses present. Viruses were recovered from five of eight chlorinated primary effluents from which fecal coliforms were not recovered by standard most-probable-number procedures. The limited volumes of such chlorinated effluents that can be tested for indicator bacteria with currently available multiple-tube and membrane filter techniques restrict the value of fecal coliforms, fecal streptococci, and even total coliforms as indicators of viruses in these effluents. Although fecal coliforms and fecal streptococci are useful indicators of viruses in effluents from which these bacteria are recovered, the absence of these bacteria and even total coliforms from disinfected effluents (in standard tests) does not assure that viruses are also absent.  (+info)

Up-regulation of NK cytotoxic activity via IL-15 induction by different viruses: a comparative study. (16/2188)

IL-15 is a recently identified cytokine that belongs to the four alpha-helix bundle cytokine family and possesses biological activities similar to those of IL-2. Its ability to induce effectors of NK activity suggests its involvement in innate immunity. In this study, we analyzed the effect of different viruses (HSV, EBV, respiratory syncitial virus, vesicular stomatitis virus, influenza virus, reovirus, and Sendai virus) on the up-regulation of NK activity in vitro. Exposure of human PBMC to the these viruses resulted in an immediate up-regulation of NK activity of PBMC via IL-15 induction; this effect was abrogated in the presence of mAbs to IL-15. Results of experiments conducted in parallel using mAbs to IL-15, as well as to other cytokines (IL-2, IL-12, IFN-gamma, and TNF-alpha), clearly indicated that IL-15 was specifically responsible for the observed effect. Furthermore, supernatants of virus-infected PBMC cultures significantly enhanced NK activity of uninfected PBMC in vitro. An increase of IL-15 protein levels 20 h postinfection was also confirmed in a bioassay using the IL-2-dependent cell line CTLL. Kinetic analysis of IL-15 mRNA expression using a semiquantitative RT-PCR revealed that the level of IL-15 messages peaked at different time points (up to 12 h) postinfection, depending on the nature of the virus. Taken together, these results suggest that the IL-15 response of the host to viral infection and the subsequent NK cell activation represent an important effector mechanism of the innate immune surveillance of the host against viral infections.  (+info)