Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038362 (stomatitis)
 8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

UV irradiation of infectious vesicular stomatitis virus was employed to study the relationship between the expression of certain viral gene functions and viral inhibition of RNA synthesis in mouse myeloma (MPC-11) cells. Viral infectivity, protein synthesis, and viral mRNA synthesis were all highly susceptible to inactivation by UV radiation; however, low levels of viral transcriptase activity were detected in vitro in virus preparations subjected to large doses of UV radiation. In sharp contrast, the capacity of vesicular stomatitis virus to shut off cellular transcription was quite resistant to UV radiation. The data presented here indicate that viral transcription is essential to inhibit host RNA metabolism, even though synthesis of viral polypeptides in the inhibited cells could not be detected. At those levels of UV radiation that inactivated all viral gene functions, except viral inhibition of cellular RNA synthesis, the only viral product detected was non-adenylated, low-molecular-weight RNA species.
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PMID:Use of UV irradiation to identify the genetic information of vesicular stomatitis virus responsible for shutting off cellular RNA synthesis. 9 Jan 65

Infection of MPC-11 mouse plasmacytoma cells by vesicular stomatitis virus results in 30 to 35% reduction in [35S]methionine incorporation into total proteins within 30 min postinfection. By 6 h postinfection, total protein synthesis is reduced by 80 to 90%. However, even by 30 min postinfection, a differential suppression of the synthesis of individual host protein is observed. The synthesis of the immunoglobin G (IgG) heavy chain (H), and, in particular, the synthesis of IgG light chain (L), is considerably more resistant to vesicular stomatitis virus-induced inhibition than is the synthesis of the non-IgG proteins as a whole; e.g., when the synthesis of non-IgG proteins was reduced by 41%, the synthesis of the H and L chains was reduced by 28 and 7%, respectively. Furthermore, these alterations in the relative synthesis of the L chain, H chain, and non-IgG are comparable to the alterations previously observed in uninfected MPC-11 cells when the overall rate of polypeptide chain initiation was selectively reduced (D.L. Nuss and G. Koch, 1976). These results are discussed in terms of the strategy of virus-directed suppression of host mRNA translation.
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PMID:Translation of individual host mRNA's in MPC-11 cells is differentially suppressed after infection by vesicular stomatitis virus. 18 15

Infection of mouse myeloma cells (MPC-11) with vesicular stomatitis (VS) virus resulted in rapid and marked reduction in cellular RNA synthesis considerably before cell viability was compromised. Mouse myeloma cells responded maximally to viral infection at a multiplicity of 1 and were considerably more se;sitive to shut-off of RNA synthesis than were mouse L cells or BHK-21 cells. This inhibition of cellular RNA synthesis was shown not to be caused by differential membrane permeability of infected and uninfected MPC-11 cells to [3H]uridine, nor was it due to greater degradation of previously synthesized RNA. VS viral infection appeared not to impede transport of newly synthesized nuclear RNA to the cytoplasm; moreover, infected cells accumulated polyadenylated mRNA at the same rate as did uninfected cells. Polyacrylamide gel electrophoresis of newly synthesized nuclear RNA demonstrated that the polydisperse nature and size distribution were not affected by VS viral infection. Isolated nuclei of infected MPC-11 cells also inhibited greatly impaired capacity to synthesize RNA despite the absence of cytoplasmic factors. Infected-cell cytosol did not inhibit transcription by uninfected-cell nuclei, nor did uninfected-cell cytosol reverse viral inhibition of nuclear transcription. Studies with alpha-amanitin revealed that VS viral infection inhibited the activity of polymerases I, II, and III, but only polymerase II was affected progressively throughout infection and to a much greater extent. These data suggest that, even at low multiplicities of infection, VS virus rapidly shuts off cellular RNA synthesis at the level of nuclear transcription.
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PMID:Inhibition of RNA synthesis in mouse myeloma cells infected with vesicular stomatitis virus. 20 71

Infection of mouse myeloma (MPC-11) cells with vesicular stomatitis virus resulted in rapid loss in activity of cellular RNA polymerases associated with nuclear chromatin. No RNA polymerase inhibitor could be detected in extracts of infected cell nuclei. Reconstitution experiments with solubilized RNA polymerases dissociated from chromatin of infected and uninfected cells demonstrated that vesicular stomatitis viral infection did not affect the ability of the polymerases to function on endogenous or exogenous templates; nor did infection alter the template capability of the chromatin. Measurement of the number of actively growing RNA chains revealed that infected cell nuclei contained fewer active polymerase units; however, the rates of RNA chain elongation were the same in nuclei from infected and uninfected cells. Quantitation of the number of polymerase units active in nuclear chromatin revealed that the alpha-amantin-sensitive polymerase II was more severely reduced by viral infection than were polymerases I and III.
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PMID:Vesicular stomatitis virus infection reduces the number of active DNA-dependent RNA polymerases in myeloma cells. 22 70

RNA synthesis by mouse myeloma (MPC-11) cells was rapidly and progressively shut off by infection with vesicular stomatitis virus temperature-sensitive (ts) mutants permissive for transcription. In sharp contrast, mutants or defective vesicular stomatitis virions restricted in transcription were incapable of causing progressive inhibition of cellular RNA synthesis even at massive multiplicities of infection. A viral product synthesized 30 to 60 min after permissive infection with tsG114(I) appeared to be essential for prolonged inhibition of RNA synthesis in cells switched up to restrictive temperature.
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PMID:Transcription of vesicular stomatitis virus is required to shut off cellular RNA synthesis. 22 26

DNA synthesis in mouse myeloma (MPC-11) cells and L cells was rapidly and progressively inhibited by infection with vesicular stomatitis virus (VSV). No significant difference in cellular DNA synthesis inhibition was noted between synchronized and unsynchronized cells, nor did synchronized cells vary in their susceptibility to VSV infection after release from successive thymidine and hydroxyurea blocks. Cellular RNA synthesis was inhibited to about the same extent as DNA synthesis, but cellular protein synthesis was less affected by VSV at the same multiplicity of infection. The effect of VSV on cellular DNA synthesis could not be attributed to degradation of existing DNA or to decreased uptake of deoxynucleoside triphosphates, nor were DNA polymerase and thymidine kinase activities significantly different in VSV-infected and uninfected cell extracts. Analysis by alkaline sucrose gradients of DNA in pulse-labeled uninfected and VSV-infected cells indicated that VSV infection did not appear to influence DNA chain elongation. Cellular DNA synthesis was not significantly inhibited by infection with the VSV polymerase mutant tsG114(I) at the restrictive temperature or by infection with defective-interfering VSV DI-011 (5' end of the genome), but DI-HR-LT (3' end of genome) exhibited initially rapid but not prolonged inhibition of MPC-11 cell DNA synthesis. DNA synthesis inhibitory activity of wild-type VSV was only slowly and partially inactivated by very large doses of UV irradiation. These data suggest that, as in the effect of VSV on cellular RNA synthesis (Weck et al., J. Virol. 30:746-753, 1979), inhibition of cellular DNA synthesis by VSV requires transcription of a small segment of the viral genome.
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PMID:Inhibition of cellular DNA synthesis by vesicular stomatitis virus. 616 31

A variant line (LV-1) of mouse myeloma MOPC 315 (IgA, lambda 2) has lost the ability to synthesize L chain. It synthesizes an altered H chain (H' chain) that is turned over intracellularly and is not secreted. Rescue of H' chain secretion can be accomplished by fusion of LV-1 to a variant of another myeloma line, MPC 11 (IgG2b, kappa), which only synthesizes a light chain. The hybrid (X-2) secretes the H' chain in a four chain structure (kappa 2 alpha' 2). In wild-type MOPC 315 cells, it was reported previously that inhibition of core sugar addition blocks the secretion of the H chain polypeptide. We have studied glycosylation in MPOC 315 wild-type, LV-1 variant, and X-2 hybrid cell lines. The ability of all three lines to add the core sugars mannose and glucosamine to heavy chain was demonstrated. Due to the instability of the H' chain in LV-1, it is difficult to assess H' chain fucosylation directly. To study fucose addition in LV-1, the enveloped virus vesicular stomatitis (VSV), which can infect the three lines, was utilized. The fucosylation and secretion of VSV glycoprotein G was discernible in all three lines; however, only LV-1 cannot activate free fucose, and instead fucosylates through conversion of the mannose intermediate. Normal fucose addition to H chain in a wild-type cell occurred immediately before secretion. The fact that degradation of H' chain in LV-1 begins before fucosylation suggests that the rescue of H' chain secretion by formation of the X-2 hybrid is due to the acquired presence of a suitable L chain rather than complementation of a sugar defect. These observations indicate that proper assembly of the polypeptide components of some secretory proteins, e.g., Ig molecules, is required for the secretion of the individual chains.
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PMID:Glycosylation and secretion of an altered immunoglobulin heavy chain in mouse myeloma MOPC 315. 629 92

Tumor-selective oncolytic vesicular stomatitis viruses (VSVs) are being evaluated in clinical trials. Here, we report that the MPC-11 murine plasmacytoma model is so extraordinarily susceptible to oncolytic VSVs that a low dose of virus leads to extensive intratumoral viral replication, sustained viremia, intravascular coagulation, and a rapidly fatal tumor lysis syndrome (TLS). Rapid softening, shrinkage and hemorrhagic necrosis of flank tumors was noted within 1-2 days after virus administration, leading to hyperkalemia, hyperphosphatemia, hypocalcemia, hyperuricemia, increase in plasma cell free DNA, lymphopenia, consumptive coagulopathy, increase in fibrinogen degradation products, decreased liver function tests, dehydration, weight loss, and euthanasia or death after 5-8 days. Secondary viremia was observed but viral replication in normal host tissues was not detected. Toxicity could be mitigated by using VSVs with slowed replication kinetics, and was less marked in animals with smaller flank tumors. The MPC-11 tumor represents an interesting model to further study the complex interplay of robust intratumoral viral replication, tumor lysis, and associated toxicities in cases where tumors are highly responsive to oncolytic virotherapy.
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PMID:Robust Oncolytic Virotherapy Induces Tumor Lysis Syndrome and Associated Toxicities in the MPC-11 Plasmacytoma Model. 2766 55

Noninvasive dual-imaging methods that provide an early readout on tumor permissiveness to virus infection and tumor cell death could be valuable in optimizing development of oncolytic virotherapies. Here, we have used the sodium iodide symporter (NIS) and 125I radiotracer to detect infection and replicative spread of an oncolytic vesicular stomatitis virus (VSV) in VSV-susceptible (MPC-11 tumor) versus VSV-resistant (CT26 tumor) tumors in BALB/c mice. In conjunction, tumor cell death was imaged simultaneously using technetium (99mTc)-duramycin that binds phosphatidylethanolamine in apoptotic and necrotic cells. Dual-isotope single-photon emission computed tomography/computed tomography (SPECT/CT) imaging showed areas of virus infection (NIS and 125I), which overlapped well with areas of tumor cell death (99mTc-duramycin imaging) in susceptible tumors. Multiple infectious foci arose early in MPC-11 tumors, which rapidly expanded throughout the tumor parenchyma over time. There was a dose-dependent increase in numbers of infectious centers and 99mTc-duramycin-positive areas with viral dose. In contrast, NIS or duramycin signals were minimal in VSV-resistant CT26 tumors. Combinatorial use of NIS and 99mTc-duramycin SPECT imaging for simultaneous monitoring of oncolytic virotherapy (OV) spread and the presence or absence of treatment-associated cell death could be useful to guide development of combination treatment strategies to enhance therapeutic outcome.
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PMID:Dual-Isotope SPECT Imaging with NIS Reporter Gene and Duramycin to Visualize Tumor Susceptibility to Oncolytic Virus Infection. 3189 Aug 67