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1.
Antiviral state against influenza virus neutralized by microinjection of antibodies to interferon-induced Mx proteins. 总被引:11,自引:2,他引:9
In mouse Mx+ cells, interferon alpha/beta induces the synthesis of the nuclear Mx protein, whose accumulation is correlated with specific inhibition of influenza viral protein synthesis. When Mx+ mouse cells are microinjected with the monoclonal anti-Mx antibody 2C12, interferon alpha/beta still induces Mx protein, but no longer inhibits efficiently the expression of influenza viral proteins as visualized by immunofluorescent labeling. However, interferon inhibition of an unrelated control virus, vesicular stomatitis virus, remains unchanged. Proteins with homology to mouse Mx protein are found in interferon-treated cells of a variety of mammalian species. In rat cells, for instance, rat interferon alpha/beta induces three Mx proteins which all cross-react with antibody 2C12 but differ in mol. wt and intracellular location, and it protects these cells well against influenza viruses. However, when rat cells are microinjected with antibody 2C12, interferon alpha/beta cannot induce an efficient antiviral state against influenza virus infection, whereas protection against vesicular stomatitis virus is not altered. These results show that both mouse and rat cells require functional Mx proteins for efficient protection against influenza virus. They further demonstrate that microinjection of antibodies is a promising way of elucidating the role of particular interferon-induced proteins in the intact cell. 相似文献
2.
Interferon-induced Mx proteins form oligomers and contain a putative leucine zipper. 总被引:14,自引:0,他引:14
K Melén T Ronni B Broni R M Krug C H von Bonsdorff I Julkunen 《The Journal of biological chemistry》1992,267(36):25898-25907
Interferons induce a number of different proteins that mediate the antiproliferative, antiviral, and immunomodulatory functions of interferons. At least three different proteins mediate the antiviral response, and one of them, Mx protein, specifically inhibits the replication of influenza virus and (vesicular stomatitis virus). Mouse and rat Mx1 proteins are nuclear, whereas other presently known Mx proteins are cytoplasmic. The cellular functions of Mx proteins are unknown, but all of them contain a consensus GTP binding site. Very little information is available on the structure and characteristics of the mouse Mx1 protein itself. For biochemical characterization, we expressed mouse Mx1 protein in a baculovirus system and purified it to homogeneity. The purified protein as well as the authentic murine cellular Mx1 protein exists in dimers and trimers in the presence of dissociating solvents, whereas in physiological buffers they form aggregates. Cross-linking experiments done on Mx-expressing cells from various species revealed that mouse, rat, and human Mx proteins exist predominantly in trimers. Amino acid sequence analysis shows that all known Mx proteins have conserved leucine repeats typical for a leucine zipper at their COOH-terminal end. In vitro translation of chimeric catechol O-methyltransferase-Mx1 gene constructs revealed that the leucine zipper domain of Mx1 protein is responsible for the oligomerization. The COOH terminus also functions as a nuclear localization signal. Microinjection of purified oligomers into the cell cytoplasm resulted in a fast accumulation of the protein in the resulted in a fast accumulation of the protein in the nucleus. Immunoelectron microscopy revealed that nuclear murine Mx1 protein exists in distinct, electron-dense structures separate from nuclear membrane, and chromatin, or nucleolus. These observations reveal that a COOH-terminal leucine zipper domain is an important structural element of all Mx proteins. Its relevance to the biology and functions of Mx proteins is presently not known. 相似文献
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Myxococcus xanthus msDNA.Mx162 exists as a complex with proteins 总被引:2,自引:0,他引:2
4.
Efficacy of chemical disinfectants against snakehead rhabdovirus 总被引:1,自引:0,他引:1
G. N. Frerichs 《Zeitschrift fur angewandte Ichthyologie》1990,6(2):117-123
The susceptibility of snakehead rhabdovirus to treatment at 20°C with 5 commercially available disinfectants was examined. No reduction in virus infectivity occurred following exposure to 5 ppm malachite green for 6 hours. Treatment of infective cell culture fluids with 2% formalin resulted in > 99.9% reduction in virus titre within 5 minutes and complete inactivation within 30 minutes, but a negligible loss in infectivity after exposure to 0.025% formalin for 1 hour. Suspensions of virus in distilled water were completely inactivated within 5 minutes by 12.5 ppm chlorine, 50 ppm iodine, or a 1:2000 dilution of a peroxygen disinfectant. In the presence of serum in infective cell culture fluids, however, > 50 ppm chlorine was required to inactivate the agent and no measurable reduction in infectivity was observed following treatment with 500 ppm iodine for 30 minutes. 相似文献
5.
cDNA structures and regulation of two interferon-induced human Mx proteins. 总被引:33,自引:2,他引:31
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M Aebi J F?h N Hurt C E Samuel D Thomis L Bazzigher J Pavlovic O Haller P Staeheli 《Molecular and cellular biology》1989,9(11):5062-5072
Human cells treated with interferon synthesize two proteins that exhibit high homology to murine Mx1 protein, which has previously been identified as the mediator of interferon-induced cellular resistance of mouse cells against influenza viruses. Using murine Mx1 cDNA as a hybridization probe, we have isolated cDNA clones originating from two distinct human Mx genes, designated MxA and MxB. In human fibroblasts, expression of MxA and MxB is strongly induced by alpha interferon (IFN-alpha), IFN-beta, Newcastle disease virus, and, to a much lesser extent, IFN-gamma, MxA and MxB proteins have molecular masses of 76 and 73 kilodaltons, respectively, and their sequences are 63% identical. A comparison of human and mouse Mx proteins revealed that human MxA and mouse Mx2 are the most closely related proteins, showing 77% sequence identity. Near their amino termini, human and mouse Mx proteins contain a block of 53 identical amino acids and additional regions of very high sequence similarity. These conserved sequences are also present in a double-stranded RNA-inducible fish gene, which suggests that they may constitute a functionally important domain of Mx proteins. In contrast to mouse Mx1 protein, which accumulates in the nuclei of IFN-treated mouse cells, the two human Mx proteins both accumulate in the cytoplasm of IFN-treated cells. 相似文献
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Interferon-induced Mx proteins in antiviral host defense 总被引:7,自引:0,他引:7
7.
Mx proteins: GTPases with antiviral activity 总被引:16,自引:0,他引:16
Mx proteins are synthesized in interferon-treated vertebrate cells. They have attracted much attention because some of them can block the multiplication of influenza A virus and certain other negative-stranded RNA viruses. Recently, Mx proteins have been shown to be GTPases with significant homology to dynamins and yeast VPS1, enzymes involved in intracellular protein trafficking. Several biochemical properties of dynamin and VPS1 are similar to those of Mx, promoting new speculation about how Mx proteins might interfere with virus multiplication. 相似文献
8.
The Mx GTPase family of interferon-induced antiviral proteins 总被引:9,自引:1,他引:8
Mx proteins are interferon-induced members of the dynamin superfamily of large GTPases. They inhibit a wide range of viruses by blocking an early stage of the replication cycle. Studies in genetically defined mouse strains highlight their powerful action in early antiviral host defence. 相似文献
9.
The interferon-inducible Mx1 protein is responsible for inborn resistance of mice to influenza. It is now recognized that this protein is a member of a family of interferon-inducible, putative GTP-binding proteins found in many organisms. Thus, these proteins, called the Mx proteins, are found in species that are naturally infected with influenza virus, and also in species that are not. Some Mx proteins display a broader antiviral profile than the one observed for Mx1 in mice. Others, however, may not be antiviral. Two recently discovered GTP-binding proteins, Vps1p in yeast and dynamin in rat, are also related to Mx1. These proteins are synthesized constitutively and serve basic cellular functions. 相似文献
10.
A functional GTP-binding motif is necessary for antiviral activity of Mx proteins. 总被引:9,自引:3,他引:9
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F Pitossi A Blank A Schrder A Schwarz P Hüssi M Schwemmle J Pavlovic P Staeheli 《Journal of virology》1993,67(11):6726-6732
Mx proteins are interferon-induced GTPases that inhibit the multiplication of certain negative-stranded RNA viruses. However, it has been unclear whether GTPase activity is necessary for antiviral function. Here, we have introduced mutations into the tripartite GTP-binding consensus elements of the human MxA and mouse Mx1 proteins. The invariant lysine residue of the first consensus motif, which interacts with the beta- and gamma-phosphates of bound GTP in other GTPases, was deleted or replaced by methionine or alanine. These Mx mutants and appropriate controls were then tested for antiviral activity, GTP-binding capacity, and GTPase activity. We found a direct correlation between the GTP-binding capacities and GTP hydrolysis activities of the purified Mx mutants in vitro and their antiviral activities in transfected 3T3 cells, demonstrating that a functional GTP-binding motif is necessary for virus inhibition. Our results, thus, firmly establish antiviral activity as a novel function of a GTPase, emphasizing the enormous functional diversity of GTPase superfamily members. 相似文献
11.
Antiviral determinants of rat Mx GTPases map to the carboxy-terminal half. 总被引:2,自引:0,他引:2
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L Johannes R Kambadur H Lee-Hellmich C A Hodgkinson H Arnheiter E Meier 《Journal of virology》1997,71(12):9792-9795
Rat Mx2 and rat Mx3 are two alpha/beta interferon-inducible cytoplasmic GTPases that differ in three residues in the amino-terminal third, which also contains the tripartite GTP-binding domain, and that differ in five residues in the carboxy-terminal quarter, which also contains a dimerization domain. While Mx2 is active against vesicular stomatitis virus (VSV), Mx3 lacks antiviral activity. We mapped the functional difference between Mx2 and Mx3 protein to two critical residues in the carboxy-terminal parts of the molecules. An exchange of either residue 588 or 630 of Mx2 with the corresponding residues of Mx3 abolished anti-VSV activity, and the introduction of the two Mx2 residues on an Mx3 background partially restored anti-VSV activity. These results are consistent with the facts that Mx2 and Mx3 have similar intrinsic GTPase activities and that the GTPase domain of Mx3 can fully substitute for the GTPase domain of Mx2. Nevertheless, the amino-terminal third containing the GTP-binding domain is necessary for antiviral activity, since an amino-terminally truncated Mx2 protein is devoid of anti-VSV activity. Furthermore, Fab fragments of a monoclonal antibody known to neutralize antiviral activity block GTPase activity by binding an epitope in the carboxy-terminal half of Mx2 or Mx3 protein. The results are consistent with a two-domain model in which both the conserved amino-terminal half and the less-well-conserved carboxy-terminal half of Mx proteins carry functionally important domains. 相似文献
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18.
Development of a DNA vaccine against hirame rhabdovirus and analysis of the expression of immune-related genes after vaccination 总被引:1,自引:0,他引:1
Intramuscular injection of Japanese flounder, Paralichthys olivaceus (average weight approximately 2 g) with 1 and 10 microg of a plasmid DNA vaccine encoding the hirame rhabdovirus (HIRRV) glycoprotein gene (pCMV-HRVg) was found to provide strong protection against HIRRV. We also conducted a real-time PCR analysis to quantify immune-related genes, e.g. MHC class Ialpha, IIalpha, IIbeta, TCR-alpha, beta1, beta2 and delta, to characterize the immune response at 1 and 7 days after DNA vaccination. In general, the copy numbers were at least 2-fold higher than those of the non-vaccinated fish. Interestingly, the gene expression of TCR beta1 and beta2 increased 1 day post-DNA vaccination, after which their copy numbers returned to levels similar to those before vaccination. These results suggest that the immune system of Japanese flounder was activated immediately after DNA immunization. 相似文献
19.
M Chambon J L Bailly H Peigue-Lafeuille 《Applied and environmental microbiology》1992,58(11):3517-3521
The activity of glutaraldehyde (GTA) against capsid proteins of poliovirus type 1 and echovirus type 25 was studied to understand the mode of action of this reagent against enteroviruses. The viruses were treated with GTA concentrations ranging from 0.005 to 0.10%. In the poliovirus particles, high-molecular-weight products were formed by 0.05% GTA, whereas in the echovirus particles, they were formed at 0.005% GTA. These products consist of complexes composed essentially of VP1 and VP3. There seemed to be differences in the composition of the complexes in the two viruses. Cross-linkings between the two polypeptides of the poliovirus capsid may be due to the accessibility to GTA of lysine residues on the loops of VP1 and VP3, which twist out from the surface of the shell. 相似文献
20.
Activity of glutaraldehyde at low concentrations against capsid proteins of poliovirus type 1 and echovirus type 25. 总被引:2,自引:2,他引:0
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The activity of glutaraldehyde (GTA) against capsid proteins of poliovirus type 1 and echovirus type 25 was studied to understand the mode of action of this reagent against enteroviruses. The viruses were treated with GTA concentrations ranging from 0.005 to 0.10%. In the poliovirus particles, high-molecular-weight products were formed by 0.05% GTA, whereas in the echovirus particles, they were formed at 0.005% GTA. These products consist of complexes composed essentially of VP1 and VP3. There seemed to be differences in the composition of the complexes in the two viruses. Cross-linkings between the two polypeptides of the poliovirus capsid may be due to the accessibility to GTA of lysine residues on the loops of VP1 and VP3, which twist out from the surface of the shell. 相似文献