Selective inhibition of herpes simplex virus glycoprotein synthesis by a benz-amidinohydrazone derivative

Campadelli-Fiume, Gabriella; Vallebona, P Sinibaldi; Cavrini, Vanni; Mannini-Palenzona, A

doi:10.1007/bf01314732

Cited by 12 publications

(18 citation statements)

References 33 publications

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“…The effect is HSV specific in the sense that the drug does not affect the glycosylation of the proteins of other viruses (Sindbis virus and paramyxoviruses). In HSV-1-infected cells, the pattern of protein synthesis in treated cells (2) cannot be differentiated from that of untreated cells.…”

Section: Discussionmentioning

confidence: 99%

“…Protein nomenclature was according to Morse et al (7). Details for harvesting cells and measuring trichloroacetic acid-precipitable radioactive material were described (2). NaDodSO4 electrophoresis of glycoproteins and proteins was on 8.5% polyacrylamide gels crosslinked with NN'-diallyl tartardiamide.…”

Section: Methodsmentioning

confidence: 99%

“…BH appears to be a selective inhibitor of herpesvirus glycosylation in that it does not affect HSV-1 protein synthesis or the glycosylation of uninfected cells, Sindbis virus, or paramyxovirus proteins (2). Studies on glycopeptide size-distribution and endo-,B-N-acetylglucosaminidase H sensitivity of HSV glycoproteins formed in the presence of BH indicated that the compound prevents high-mannose oligosaccharide addition to proteins (3).…”

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confidence: 99%

“…rivative [lH-benz[flindene-1,3(2H)-dionebis(amidinohydrazone)], designated benzhydrazone (BH), inhibits glycosylation of the major herpes simplex virus type 1 (HSV-1) glycoproteins (1,2). BH appears to be a selective inhibitor of herpesvirus glycosylation in that it does not affect HSV-1 protein synthesis or the glycosylation of uninfected cells, Sindbis virus, or paramyxovirus proteins (2).…”

mentioning

confidence: 99%

“…BH causes, therefore, an early block in the asparagine-linked N-glycosylation process similar to that induced by tunicamycin. Along with glycosylation, BH inhibits herpesvirus-induced cell fusion and reduces the yield of infectious virus (2).…”

mentioning

confidence: 99%

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Characterization of a herpes simplex virus type 1 mutant resistant to benzhydrazone, a selective inhibitor of herpesvirus glycosylation.

Tognon¹,

Manservigi²,

Cavrini³

et al. 1984

Proc. Natl. Acad. Sci. U.S.A.

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Benzhydrazone [BH;indene-1,3(2H)-dionebis(amidinohydrazone)] significantly inhibits glycosylation of proteins, but only in cells infected with herpes simplex virus. We report on a herpes simplex virus type 1 (HSV-1) mutant resistant to BH. A syncytium-inducing mutant designated HSV-1(13)S11 was found to be biochemically resistant to BH in that [14C]glucosamine incorporation was not inhibited in infected HEp-2 cells exposed to the drug. Intertypic recombinants were obtained which showed that BH resistance is encoded in the DNA of the mutant virus and may be transferred into the genome of BH-sensitive HSV. In the recombinants the biochemical resistance marker segregated from the syncytial marker, suggesting that the two markers probably map in different loci. The BH-resistant mutant did not complement wild-type BH-sensitive HSV-1 and -2. Furthermore, resistance was apparent in HEp-2 but not in Vero cells. The paper discusses the hypothesis that inhibition of glycosylation of HSV proteins is the consequence of modification or selective transport of BH involving a HSV gene product. ing intertypic recombinants, we observed that BH resistance is encoded in HSV-1(13)S11 DNA and may be transferred from the genome of the resistant mutant into the genome of HSV-2(G).MATERIALS AND METHODS Materials. BH was synthesized as previously described (1).Viruses and Cells. The BH-resistant (BHR) mutant HSV-1(13)S11 is a Syn-mutant selected from HEp-2 cell cultures infected with stocks obtained after 5-bromodeoxyuridine mutagenesis of the non-syncytium-inducing (Syn') HSV-1(13) (4); isolation and selection were as described for HSV-1(13)B4 (5). HSV-1(HFEM)H6 was described (6). Glycoprotein and Protein Synthesis. Labeling media for glycoproteins and proteins consisted, respectively, of minimal essential medium containing '/2 the usual concentration of glucose and [14C]glucosamine (2-3 ,uCi/ml, 50 mCi/mmol, the Radiochemical Center, Amersham; 1 Ci = 37 GBq) or minimal essential medium containing V/1o the usual concentration of methionine and [35S]methionine (25 ,uCi/ml, >400 Ci/mmol, New England Nuclear). Glycoproteins were labeled between 14 and 20 hr after infection. a polypeptides were detected by exposing cells to cycloheximide (5 ,ug/ml) from 1 hr before virus adsorption to 5 hr after infection and by labeling for 20 min after cycloheximide removal. , and y polypeptides were labeled from 5 to 7 and from 15 to 18 hr after infection, respectively. Protein nomenclature was according to Morse et al. (7). Details for harvesting cells and measuring trichloroacetic acid-precipitable radioactive material were described (2). NaDodSO4 electrophoresis of glycoproteins and proteins was on 8.5% polyacrylamide gels crosslinked with NN'-diallyl tartardiamide.Intertypic Marker Transfer. Intertypic marker transfer was done essentially as described (8,9). Approximately 1 ,g of HSV-1(13)S11 DNA digested with HindIII was mixed with 0.5 ,ug of intact HSV-2(G) DNA and the mixture was used to transfect rabbit skin cells. 2440The publication co...

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Characterization of a herpes simplex virus type 1 mutant resistant to benzhydrazone, a selective inhibitor of herpesvirus glycosylation.

Tognon¹,

Manservigi²,

Cavrini³

et al. 1984

Proc. Natl. Acad. Sci. U.S.A.

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Study of herpes simplex virus type 1 populations obtained from recurrences and primary infections

Mannini-Palenzona

Bartoletti

Foà-Tomasi

et al. 1985

Journal of Medical Virology

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The analysis of 23 clinical isolates of herpes simplex virus type 1 (HSV-1) showed that 15 of 15 isolates that had undergone a few passages in tissue culture (fresh isolates) and two of eight isolates that had never been passaged (new isolates) were composed of a mixed population with respect to plaque morphology in Vero cells. Cloning and characterization of 10 large plaque viruses (L variants) and nine small plaque viruses (S variants), obtained from seven different isolates, showed the following. BamHI DNA restriction patterns of the L and the S variants from a single isolate differed only with respect to the electrophoretic mobility of the fragments that contain reiteration of specific sequences; they did not differ regarding the presence or the absence of restriction endonuclease cleavage sites. The L and S variants differed with respect to the electrophoretic profiles of infected cell glycoproteins, thermosensitivity of growth and plaquing efficiency at 39 degrees C, and, at least in the case of the two couples of variants that we tested, pathogenicity for the mouse. The hypothesis that the L variants might arise from the S variant during in vivo replication is discussed.

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5-Propyl-2-deoxyuridine induced interference with glycosylation in herpes simplex virus infected cells

Olofsson

Sjöblom

Hellstrand

et al. 1993

Archives of Virology

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In herpes simplex virus-infected (HSV) cells, the antiviral nucleoside analogue 5-n-propyl-2'-deoxyuridine (PdU) may, under certain circumstances, induce a pattern of interference with late steps in formation of N-linked glycans, resulting in increased availability of viral glycoproteins for neutralizing antibodies. The PdU-induced changes in N-linked glycans, released by pronase digestion of the HSV-specified glycoprotein gC-1, were investigated by using lectin affinity chromatography and Bio-Gel P6 gel filtration of glycans, radiolabelled with [3H]galactose or [3H]glucosamine. PdU-treatment of HSV-infected cells totally inhibited addition of sialic acid and reduced the amount of galactose incorporated into N-linked glycans by 70%. In addition, the PDU-treatment caused a decrease in oligosaccharides with affinity for Phaseoulus vulgaris leuco-agglutinin and erythro-agglutinin, and an increase in Lens culinaris lectin (LCA)-binding oligosaccharides, suggesting a PdU-induced shift from multi-branched to moderately branched structures. This shift was also found in HSV-infected B16 mouse melanoma cells, where the large content of multi-branched oligosaccharides contributes to the metastatic potential. The LCA-binding glycans from PdU-treated cells were smaller and contained less galactose units than corresponding structures from untreated cells. In a cell-free system, PdU 5'-monophosphate inhibited the translocation of UDP-GlcNAc, and, to a smaller extent, also the translocation of UDP-galactose into Golgi vesicles, suggesting that nucleotide sugar translocation is one important target for the PdU-induced interference with glycosylation in HSV-infected cells.

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Selective inhibition of herpes simplex virus glycoprotein synthesis by a benz-amidinohydrazone derivative

Cited by 12 publications

References 33 publications

Characterization of a herpes simplex virus type 1 mutant resistant to benzhydrazone, a selective inhibitor of herpesvirus glycosylation.

Characterization of a herpes simplex virus type 1 mutant resistant to benzhydrazone, a selective inhibitor of herpesvirus glycosylation.

Study of herpes simplex virus type 1 populations obtained from recurrences and primary infections

5-Propyl-2-deoxyuridine induced interference with glycosylation in herpes simplex virus infected cells

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