Characterization of an herpes simplex virus type 2 mutant, which is resistant to acycloguanosine and causes fusion of BSC1 cells

Katz, Ehud; Margalith, Eva

doi:10.1007/bf01314705

Cited by 9 publications

(9 citation statements)

References 34 publications

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“…Since a drug-resistant virus may appear in infected cells during the growth of the wild-type strain, our data (table 1) suggest that the wildtype strain does not suppress the growth of such a virus in the absence of the drug but on the contrary, it even slightly enhances its growth. However, in the presence of ACV the growth of both viruses was completely inhibited (table 1), most probably due to the high thymidine kinase activity induced by the wild-type strain in these cells and which activated ACV [4]. A potential practical aspect based on our present study is that the use of ACV during antiherpes therapy may greatly reduce the chances of the appearance and replication of ACV-resistant mutants, since the yield of the herpesviruses under these conditions is highly reduced due to the activation of ACV by the thmyidine kinase of the wild-type virus.…”

Section: Discussionmentioning

confidence: 99%

“…The HSV-2 Curtis strain, and the ACV-resistant mutant HSV-2-ACV R derived and plaque-purified from it [4], were used. The G strain of HSV-2 and its HG52 mutant (UL41 -) were kindly provided by R.D.…”

Section: Virusesmentioning

confidence: 99%

“…When our laboratory stock of the herpes simplex virus type 2 (HSV-2) Curtis strain was plaqued in BS-C-1, approximately 2% of the virus population, which had not previously been exposed to ACV, was able to form plaques in the presence of 100 ÌM of the drug. One of these drug-resistant viruses was plaque-purified (HSV-2-ACV R ) and was found to induce low levels of thymidine kinase activities in the infected cells, while its viral DNA polymerase activity was normal [4]. The appearance and persistence of ACV-resistant HSV mutants in patients are difficult to be followed, but they were extensively examined in a mouse model [5][6][7].…”

Section: Introductionmentioning

confidence: 99%

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Co-Infection of Acyclovir-Resistant and Acyclovir-Sensitive Herpes simplex Type 2 Virus Strains in BS-C-1 Cells

Keywan

Katz²

1999

Intervirology

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Co-infection of BS-C-1 cells by the herpes simplex virus type 2 (HSV-2) Curtis strain with its acyclovir (ACV)-resistant mutant (HSV-2-ACV^R), resulted in a severalfold increase in virus yield, as compared to a single infection. On the other hand, when two viruses (G strain and HSV-2-ACV^R) belonging to different strains of HSV-2 were involved, their growth was significantly inhibited; the decrease in the titer of the second virus to infect the cells was greater when its infection took place at later times following infection by the first. This inhibition was not due to the shut-off of host cell protein synthesis caused by the first virus, since an HSV-2 mutant which is unable to inhibit the protein synthesis of the host cell was still capable of efficiently inhibiting the growth of the superinfecting virus.

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Section: Discussionmentioning

confidence: 99%

Section: Virusesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Co-Infection of Acyclovir-Resistant and Acyclovir-Sensitive Herpes simplex Type 2 Virus Strains in BS-C-1 Cells

Keywan

Katz²

1999

Intervirology

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“…The results (Table 4) show that these activities were quite similar to those of cells infected with the wild-type strains. However, the level of thymidine kinase in BSC1 cells infected with HSV-2-ACG, which is a thymidine kinase-deficient mutant (15), was significantly lower and exhibited the low enzyme activity of uninfected cells (Table 4).…”

Section: And Methodsmentioning

confidence: 99%

“…Stocks of HSV-1 (HF strain) and HSV-2 (Curtis strain), the mutants HSV-1-ACG (E. Katz, unpublished) and HSV-2-ACG (15), and poliomyelitis virus type 1 were prepared in BSC1 cells with M199 medium containing 2% FCS. The cultures were harvested 24 h postinfection (p.i.)…”

Section: And Methodsmentioning

confidence: 99%

Antiviral activity of SK&F 21681 against herpes simplex virus

Katz¹,

Margalith²

1984

Antimicrob Agents Chemother

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SK&F 21681 (3,10-dimethyl-10-H-s-triazolo[4',3':2,3]-as-triazino- [5,6-b]indole) is an inhibitor of the growth of herpes simplex viruses types 1 and 2 at a concentration of 60 ,ug/ml. It inhibits the synthesis of the viral DNA and the formation of virus particles, although the viral polypeptide synthesis is not significantly affected by this compound. Mutants of herpes simplex viruses types 1 and 2 which are able to grow in the presence of SK&F 21681 were isolated. They induced normal levels of thymidine kinase and DNA polymerase activities in the infected cells and did not show resistance to either 9-[2-hydroxyethoxymethyl] guanine or phosphonoacetic acid.The goal of antiviral chemotherapy is the discovery of highly selective compounds which are capable of inhibiting the growth of the virus while exerting minimal effects on the host cell. A specific antiviral drug will usually show a narrow antiviral spectrum, and it will be possible to isolate virus mutants which are resistant to this drug.Isatin-3-thiosemicarbazone exhibits antiviral activity, mainly against poxviruses (2, 19). A group of 3-substituted triazinoindoles, which are structurally related to isatin thiosemicarbazone, inhibit the growth of several rhinoviruses (7, (Fig. 1) is included in this group.The present study reports the selective antiviral activity of SK&F 21681 against herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) and describes the isolation and characteristics of mutants of these two viruses, which are able to grow in the presence of SK&F 21681, at concentrations which are inhibitory for the wild-type strains.( Virus. Stocks of HSV-1 (HF strain) and HSV-2 (Curtis strain), the mutants HSV-1-ACG (E. Katz, unpublished) and HSV-2-ACG (15), and poliomyelitis virus type 1 were prepared in BSC1 cells with M199 medium containing 2% FCS. The cultures were harvested 24 h postinfection (p.i.) and stored at -70°C. The stock of vaccinia virus (WR strain) was prepared in BGM cells and kept at -20°C.Virus infection. Monolayers of BSC1 cells in plastic petri dishes 5 cm in diameter were infected with 0.3 ml of virus suspension. After 1 h at 37°C, the cultures were washed with buffered saline, and S ml of M199 medium supplemented with 2% FCS was added.Plaque assay. Confluent monolayers of BGM cells in plastic petri dishes 5 cm in diameter were infected with 0.3 ml of virus dilutions. After adsorption for 1 h at 37°C, the cultures were overlaid with Eagle minimal essential medium * Corresponding author. supplemented with 0.7% Noble agar (Difco Laboratories, Detroit, Mich.) and 5% FCS. On the third day p.i. for HSV-2 and poliomyelitis virus and on the fifth day for HSV-1 and vaccinia virus, the cultures were fixed withr20% Formalin in buffered saline, pH 7.4, and stained with crystal violet (0.1%).Isolation of virus particles. Cultures which were labeled with [3H]thymidine (3 ,uCilml) starting at 2 h p.i. were harvested 20 h later. The cells were suspended in 0.6 ml of RSB (0.01 M KCl, 0.0015 M MgCl2, 0.01 M Tris, pH 7.7) and sonicated for 1 min in ...

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Synthetic purine nucleoside analogues

Holý¹

1985

Approaches to Antiviral Agents

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Characterization of an herpes simplex virus type 2 mutant, which is resistant to acycloguanosine and causes fusion of BSC1 cells

Cited by 9 publications

References 34 publications

Co-Infection of Acyclovir-Resistant and Acyclovir-Sensitive Herpes simplex Type 2 Virus Strains in BS-C-1 Cells

Co-Infection of Acyclovir-Resistant and Acyclovir-Sensitive Herpes simplex Type 2 Virus Strains in BS-C-1 Cells

Antiviral activity of SK&F 21681 against herpes simplex virus

Synthetic purine nucleoside analogues

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