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In 2007, numerous hamadryas baboons (Papio hamadryas) died suddenly in an aviary of a primate institute in Sochi, Russia, in the absence of prior clinical signs. Necropsies were suggestive of encephalomyocarditis virus infection, ...
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In 2007, numerous hamadryas baboons (Papio hamadryas) died suddenly in an aviary of a primate institute in Sochi, Russia, in the absence of prior clinical signs. Necropsies were suggestive of encephalomyocarditis virus infection, but RT-PCR assays with commonly used primers were negative. Here we report the histopathological results obtained during necropsies and the isolation and genomic characterization of a divergent strain of encephalomyocarditis virus 1 (EMCV-1) from heart tissue of one of the succumbed hamadryas baboons. Phylogenetic analysis indicates that the isolated virus belongs to the newly proposed EMCV-1 lineage G, which clusters alongside lineage C ("Mengo virus"). This study is the first report describing a lineage G strain of EMCV-1 as the etiological agent of a lethal disease outbreak among captive nonhuman primates in Europe.
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A foot-and-mouth disease virus mutant which is stable at pH 6.4 has been isolated from a virus of serotype A. In contrast to the parent (P) virus, which gave a mixture of large and small plaques in BHK21 cells and in a bovine kidn...
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A foot-and-mouth disease virus mutant which is stable at pH 6.4 has been isolated from a virus of serotype A. In contrast to the parent (P) virus, which gave a mixture of large and small plaques in BHK21 cells and in a bovine kidney cell line, the acid-resistant (AR) virus gave small plaques which did not increase markedly in size after 24 hr. The infectivity titer of the acid-resistant virus was about 100-fold lower in suckling mice than in BHK21 cells, whether the inoculation was made intraperitoneally or intracerebrally, whereas the parent virus gave similar titers in both systems. Furthermore, in mice the AR virus reached its end point two to three times more slowly. The diameter of the AR virus was almost 20% less than that of the P virus and it had a more distinct topography, but the two viruses cosedimented in sucrose gradients. However, the buoyant density in CsCl of the AR virus was slightly lower (1.42 compared with 1.43 g/cc) in coruns. The RNAs and capsid proteins of the two viruses gave similar profiles in sucrose gradients and by SDS-PAGE, respectively. However, isoelectric focusing of the capsid proteins revealed considerable differences between the two viruses. Whereas the P virus gave four protein bands, corresponding to VP1-VP4, the AR virus gave one band for VP4, two for VP3, two for VP2, and four for VP1. Sequence analysis of the genes coding for the capsid protein regions of the two viruses showed four changes (one silent), resulting in an Ala-3 --> Ser substitution in VP1 and Glu-131 --> Lys and Asp-133 --> Ser substitutions in VP2. (C) 1995 Academic Press, Inc.
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Introduction: Oncolytic viruses are genetically engineered viruses that target myeloma-affected cells by detecting specific cell surface receptors (CD46, CD138), causing cell death by activating the signaling pathway to induce apo...
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Introduction: Oncolytic viruses are genetically engineered viruses that target myeloma-affected cells by detecting specific cell surface receptors (CD46, CD138), causing cell death by activating the signaling pathway to induce apoptosis or by immune-mediated cellular destruction. Areas covered: This article summarizes oncolytic virotherapy advancements such as the therapeutic use of viruses by targeting cell surface proteins of myeloma cells as well as the carriers to deliver viruses to the target tissues safely. The major classes of viruses that have been studied for this include measles, myxoma, adenovirus, reovirus, vaccinia, vesicular-stomatitis virus, coxsackie, and others. The measles virus acts as oncolytic viral therapy by binding to the CD46 receptors on the myeloma cells to utilize its surface H protein. These H-protein and CD46 interactions lead to cellular syncytia formation resulting in cellular apoptosis. Vesicular-stomatitis virus acts by downregulation of anti-apoptotic factors (Mcl-2, BCL-2). Based upon the published literature searches till December 2020, we have summarized the data supporting the advances in viral oncolytic for the treatment of MM. Expert opinion: Oncolytic virotherapy is an experimental approach in multiple myeloma (MM); many issues need to be addressed for safe viral delivery to the target tissue
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The crystal structure of Seneca Valley Virus-001 (SVV-001), the representative member of a new genus, Senecavirus, is reported at 2.3 angstrom resolution. SVV-001 is the first naturally occurring nonpathogenic picornavirus shown t...
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The crystal structure of Seneca Valley Virus-001 (SVV-001), the representative member of a new genus, Senecavirus, is reported at 2.3 angstrom resolution. SVV-001 is the first naturally occurring nonpathogenic picornavirus shown to mediate selective cytotoxicity towards tumor cells with neuroendocrine cancer features. The nonsegmented (+) ssRNA genome of SVV-001 shares closest sequence similarity with the genomes of the members of Cardiovirus. The overall tertiary structure of VP1-VP4 subunits is conserved with the exception of loops, especially those of VP1 that show large deviations relative to the members of the cardioviruses. The surface loops of VP1 and VP2 are predicted to mediate cell tropism of SVV-001. In addition, the organization of the packaged nucleic acid density indicates that certain regions of VP2 and VP4 interact closely with the packaged nucleic acid.
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It has been reported that co-delivery of IL-12 DNA with a DNA vaccine further enhances antigen (Ag)-specific protective immunity in pathogenic challenge models. However. the enhancing effects of antibody by IL-12 have been controv...
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It has been reported that co-delivery of IL-12 DNA with a DNA vaccine further enhances antigen (Ag)-specific protective immunity in pathogenic challenge models. However. the enhancing effects of antibody by IL-12 have been controversial. To clarify this issue, we constructed an IL-12 expression vector, co-immunized IL-12 DNA with an encephalomycocarditis virus (EMCV)-D VPI plasmid vaccine, and then evaluated immune modulatory effects and protection against lethal EMCV-K challenge. We observed that VP1-specific IgG production, as well as seroconversion rates, were significantly enhanced by IL-12 co-injection. indicating that IL-12 can enhance antibody responses in this model system. In particular, co-injection with VPI plus IL-12 DNA into the same leg enhanced systemic Ag-specific Ige production to a significantly greater extent than either the separate leg injection of VPI and IL-12 DNA or VPI DNA vaccine alone. This suggests that local co-expression of IL-12 along with antigens is more important for enhanced antibody production. Furthermore, IgG2a isotype was significantly enhanced by IL-12 DNA co-injection. indicating a Th1 bias. In addition, co-delivery of IL-12 DNA was demonstrated to enhance VP1-specific Th cell proliferative responses. When animals were challenged with a lethal dose of EMCV-K, IL-12 DNA-co-immunized animals exhibited enhanced survival, as compared to VP1 DNA vaccine alone. These studies suggest that IL-12 plays an important role in increasing Ag-specific Th1 type antibody and cellular responses, resulting in enhanced protection against lethal EMCV-K challenge.
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The crystal structure of the Glu-105 --> Gly mutant of catabolic ornithine transcarbamoylase (OTCase; carbamoyl phosphate + L-ornithine = orthophosphate + L-citrulline, EC 2.1.3.3) from Pseudomonas aeruginosa has been determined a...
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The crystal structure of the Glu-105 --> Gly mutant of catabolic ornithine transcarbamoylase (OTCase; carbamoyl phosphate + L-ornithine = orthophosphate + L-citrulline, EC 2.1.3.3) from Pseudomonas aeruginosa has been determined at 3.0-Angstrom resolution, This mutant is blocked in the active R (relaxed) state, The structure was solved by the molecular replacement method, starting from a crude molecular model built from a trimer of the catalytic subunit of another transcarbamoylase, the extensively studied aspartate transcarbamoylase (ATCase) from Escherichia coil, This model was used to generate initial low-resolution phases at 8-Angstrom resolution, which were extended to 3-Angstrom by noncrystallographic symmetry averaging, Four phase extensions were required to obtain an electron density map of very high quality from which the final model was built, The structure, including 4020 residues, has been refined to 3-Angstrom, and the current crystallographic R value is 0.216, No solvent molecules have been added to the model, The catabolic OTCase is a dodecamer composed of four trimers organized in a tetrahedral manner. Each monomer is composed of two domains, The carbamoyl phosphate binding domain shows a strong structural homology with the equivalent ATCase part. In contrast, the other domain, mainly implicated in the binding of the second substrate (ornithine for OTCase and aspartate for ATCase) is poorly conserved, The quaternary structures of these two allosteric transcarbamoylases are quite divergent: the E. coil ATCase has pseudo-32 point-group symmetry, with six catalytic and six regulatory chains; the catabolic OTCase has 23 point-group symmetry and only catalytic chains. However, both enzymes display homotropic and heterotropic cooperativity. [References: 35]
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