Syncytium formation is induced in the murine neuroblastoma cell cultures which produce pathogenic type G proteins of the rabies virus

Morimoto, Kanehisa; Ni, Yajin; Kawai, Akihiko

doi:10.1016/0042-6822(92)90696-m

Cited by 30 publications

(17 citation statements)

References 44 publications

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“…Other studies showed that pathogenic viruses apparently could use receptors or routes of entry different from those used by their nonpathogenic derivatives (10,26). Fusion of rabies virus-infected cells may also be an important pathogenetic mechanism (37). Changes in the surface envelope gly- VOL.…”

Section: Discussionmentioning

confidence: 99%

Vesicular Stomatitis Virus Glycoprotein Is a Determinant of Pathogenesis in Swine, a Natural Host

Martı́nez

Rodrı́guez

Jiménez

et al. 2003

J Virol

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There are two major serotypes of vesicular stomatitis virus (VSV), Indiana (VSIV) and New Jersey (VSNJV). We recovered recombinant VSIVs from engineered cDNAs that contained either (i) one copy of the VSIV G gene (VSIV-GI); (ii) two copies of the G gene, one from each serotype (VSIV-GNJGI); or (iii) a single copy of the GNJ gene instead of the GI gene (VSIV-GNJ). The recombinant viruses expressed the appropriate glycoproteins, incorporated them into virions, and were neutralized by antibodies specific for VSIV (VSIV-GI), VSNJV (VSIV-GNJ), or both (VSIV-GNJGI), according to the glycoprotein(s) they expressed. All recombinant viruses grew to similar titers in cell culture. In mice, VSIV-GNJ and VSIV-GNJGI were attenuated. However, in swine, a natural host for VSV, the GNJ glycoprotein-containing viruses caused more severe lesions and replicated to higher titers than the parental virus, VSIV-GI. These observations implicate the glycoprotein as a determinant of VSV virulence in a natural host and emphasize the differences in VSV pathogenesis between mice and swine

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Section: Discussionmentioning

confidence: 99%

Vesicular Stomatitis Virus Glycoprotein Is a Determinant of Pathogenesis in Swine, a Natural Host

Martı́nez

Rodrı́guez

Jiménez

et al. 2003

J Virol

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“…After many trials in culture, we found that sodium butyrate (NaB) could induce the modification of cellular functions required for the antigenic as well as functional maturation of G protein. This idea has hidden for 10 years since our previous study, in which NaB induced the functional G protein production in a neuroblastoma cell line (21). The present study suggests that functional maturation of the rabies virus G protein to acquire pH-dependent cell-fusing activity was correlated with its structural maturation to form the 1-30-44 epitope, which could be achieved in the NaB-treated BHK-21 cells.…”

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confidence: 62%

“…Our previous studies on the rabies virus G protein synthesis also demonstrated that the recombinant vaccinia virus (RVV-T7)-mediated G cDNA expression resulted in production of functional G proteins in terms of acquisition of the low pH-dependent fusogenic activity, while such activity was not associated with the G gene products that were expressed without the help of RVV-T7 (16,21). From our studies on the properties of the rabies virus G protein produced in the G cDNA-transfected cells in culture (16,21), we assume that maturation of the G protein was blocked when the G gene was expressed in the absence of other rabies viral gene functions. We further assume that certain modification of cellular condition(s) is required for the G protein maturation, the modification that would be provided by the infection with the vaccinia virus as well as rabies virus (16).…”

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confidence: 99%

Studies on the Conditions Required for Structural and Functional Maturation of Rabies Virus Glycoprotein (G) in G cDNA‐Transfected Cells

Sakai

Kankanamge

Shoji

et al. 2004

Microbiology and Immunology

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The spike projections of the rabies virion are composed of homotrimers of a single type of virus-coded glycoprotein (G) composed of 505 amino acids (1,11,35). The spike G proteins are involved in both the receptor recognition and binding to receptor molecules as well as in the low pH-dependent membrane fusion that occurs in the endosomes for releasing the viral ribonucleoprotein into the cytoplasm (30,31,34). As suggested from the experiments in which an amino acid substitution at position 333 of G protein strongly affected the viral neurovirulent nature (4,28,32), certain viral G protein function(s) might be involved in the selective viral invasion into and/or replication in the limited regions and/or the limited cell species in the brain. But, molecular and cellular mechanisms of viral neurovirulence also remain obscure yet.Precise mechanisms of the receptor recognition by rabies virus G protein as well as the low pH-dependent envelope fusion remain unclear yet (6, 7). By using Abstract: When the rabies virus G cDNA was expressed with the help of T7 RNA polymerase provided by a recombinant vaccinia virus (RVV-T7), functional G proteins were produced in terms of their ability to induce low pH-dependent syncytium formation and the formation of conformational epitopes, including the acid-sensitive epitope recognized by mAb #1-30-44. Such an ability and the 1-30-44 epitope formation, however, were not associated with the G gene products when G cDNA was expressed without the help of RVV-T7 using a tetracycline-regulated expression vector (pTet-G), although they were normally transported to the surface of established G protein-producing BHK-21 (G-BHK) cells. But, when the G-BHK cells were treated with 2.5 mM sodium butyrate (NaB) after the removal of tetracycline, we could observe not only a much increased frequency of G protein-producing cells, but also the greatly enhanced maturation of the protein. Another short acylate, sodium propionate (NaP), similarly induced increased G protein synthesis at a concentration of 2.5 mM as NaB; however, such proteins were mostly not endowed with the fusion activity nor the 1-30-44 epitope, while NaP at a higher concentration as 5.0 mM did induce similarly the increased production and enhanced maturation of G protein, including the 1-30-44 epitope formation. From these results, we conclude that functional maturation of G protein to acquire fusogenic activity is correlated with 1-30-44 epitope formation, and 2.5 mM NaB not only stimulates G protein production, but also provides such cellular conditions as are required for the structural and functional maturation of the protein.

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“…Amino acid substitution at position 333 is known to affect the neuropathogenicity of rabies virus. Putative fusion domain (I) is a region which is rough homologous to the tentatively assigned low pH-dependent fusion domain of VSV G protein (8,9,39), and the putative fusion domain (II) is a sequence which resembles the fusion domain of Sendai virus F protein and other pH-independent fusion active viral proteins (24). Ϫ: N-linked glycosylation site at Asn-319.…”

Section: Discussionmentioning

confidence: 99%

Mapping of the Low pH‐Sensitive Conformational Epitope of Rabies Virus Glycoprotein Recognized by a Monoclonal Antibody #1‐30‐44

Kankanamge

Irie

Mannen

et al. 2003

Microbiology and Immunology

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Monoclonal antibody (mAb) #1‐30‐44 recognized an acid‐sensitive conformational epitope of rabies virus glycoprotein (G). The antigenicity of G protein exposed on the cell surface was lost when the infected cells were exposed to pH 5.8. By comparing the deduced amino acid sequence of G protein between the HEP‐Flury strain and the epitope‐negative CVS strain as well as the mAb‐resistant escape mutants, two distant sites that contained Lys‐202 and Asn‐336 were shown to be involved in the epitope formation. Lys‐202 is located in the so‐called neurotoxin‐like sequence, while Asn‐336 is included in antigenic site III and is very near the amino acid at position 333, which is known to affect greatly the neuropathogenicity of rabies virus when changed. Consistent with this finding, antigenicity of a neurovirulent revertant of the HEP‐Flury strain, in which Gln‐333 of G protein was replaced by Arg, was also affected as shown by its greatly decreased reactivity with mAb #1‐30‐44 compared to that of the original avirulent HEP virus. Based on these results, we hypothesize that the neurotoxin‐like domain and some amino acids in antigenic site III come into contact with each other to form a conformational epitope for mAb #1‐30‐44, and such a configuration would be lost when exposed to acidic conditions to perform a certain low pH‐dependent function of G protein.

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Syncytium formation is induced in the murine neuroblastoma cell cultures which produce pathogenic type G proteins of the rabies virus

Cited by 30 publications

References 44 publications

Vesicular Stomatitis Virus Glycoprotein Is a Determinant of Pathogenesis in Swine, a Natural Host

Vesicular Stomatitis Virus Glycoprotein Is a Determinant of Pathogenesis in Swine, a Natural Host

Studies on the Conditions Required for Structural and Functional Maturation of Rabies Virus Glycoprotein (G) in G cDNA‐Transfected Cells

Mapping of the Low pH‐Sensitive Conformational Epitope of Rabies Virus Glycoprotein Recognized by a Monoclonal Antibody #1‐30‐44

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