acyclovir and Cell-Transformation--Viral

Topics: Acyclovir; Cell Transformation, Viral; Herpesviridae Infections; Herpesvirus 3, Human; Humans; Microbial Sensitivity Tests; Simplexvirus

In this randomized double-blind and placebo controlled trial of 6 months' prophylaxis with acyclovir (ACV) in 42 bone marrow transplant (BMT) recipients, patients receiving ACV had fewer herpes simplex virus (HSV) and varicella-zoster virus (VZV) infections during the prophylaxis compared to the placebo treated patients (P less than 0.05). During the first 6 months after the prophylaxis had been discontinued the frequency of clinical HSV reactivations was low both in the ACV (1/13) and in the placebo (1/13) treated patient groups. Altogether the ACV treated patients had significantly fewer HSV reactivations during the first year after BMT (P less than 0.05). The HSV-specific lymphocyte proliferation response was also lower in the ACV treated group at 3, 6 and 12 months after BMT (P less than 0.05). VZV infections recurred rather frequently, however, after discontinuation of ACV prophylaxis. Therefore no difference was found in the number of VZV infections during the first year after BMT. The VZV-specific lymphocyte proliferation response was significantly lower in the ACV treated group only at 6 months (P less than 0.05). ACV prophylaxis had no effect on the frequency of CMV infections; CMV-specific lymphocyte proliferative responses were not decreased.

Topics: Actuarial Analysis; Acyclovir; Antigens, Viral; Bone Marrow Transplantation; Cell Transformation, Viral; Child; Child, Preschool; Clinical Trials as Topic; Double-Blind Method; Graft vs Host Disease; Herpes Simplex; Humans; Lymphocyte Activation; Random Allocation; Simplexvirus

To evaluate the effect of acyclovir (ACV) therapy on the cellular immune response, we sequentially followed 43 patients with culture-proven first episodes of genital herpes simplex virus (HSV) infection. Twenty-three patients who were treated with ACV and 20 who received placebo had blood obtained weekly during the first 6 weeks after onset of lesions and had their in vitro lymphocyte transformation (LT) response to inactivated HSV antigens measured. The mean stimulation index to HSV antigens at week 3 among patients treated with systemic ACV was 3.5 +/- 0.64 compared to 18.4 +/- 6.89 in their placebo-treated counterparts (P less than 0.05). The mean time to the development of the peak LT response to HSV antigens was 4.3 weeks in systemic-treated versus 3.4 in placebo-treated patients (P less than 0.05). The time to the development of the peak in vitro LT response to HSV antigens and the height of that response were, however, similar between topical ACV- and topical placebo-treated patients. The geometric mean HSV-2-neutralizing titer in convalescent sera was 5.4 in recipients of systemic ACV compared to 10.0 in patients treated with systemic placebo (P less than 0.05). The LT response to HSV antigen was also measured at the first recurrence in 11 patients. No differences were found in the time to first recurrence, lesion duration, number of lesions, or mean stimulation index response to inactivated HSV antigens between the six patients treated with systemic ACV during their primary episode and the five given placebo during their primary episode. Systemic ACV therapy appears to diminish the peak in vitro LT response to inactivated HSV antigens as well as to delay the time to development of that peak response. However, the cell-mediated immune response to subsequent episodes appears similar.

Topics: Acyclovir; Administration, Topical; Antibody Formation; Cell Transformation, Viral; Female; Herpes Simplex; Humans; In Vitro Techniques; Lymphocyte Activation; Male; Recurrence; Simplexvirus; Time Factors

B lymphoblastoid cell-lines (BLCL), generated by exposure of PBMC to a laboratory strain of EBV, are commonly utilized in the preparation of T cells used for immunotherapy. Although most B cells are latently infected, BLCL contain a subset of cells that harbor infectious virus, which could be released into the infusion product during preparation. To reduce this known risk, laboratories have pretreated BLCL for > or = 14 days with 100 microM acyclovir (ACV), an inhibitor of viral DNA polymerase, prior to use. We tested the effectiveness of ACV in preventing the release of infectious virus from irradiated fresh and previously frozen BLCL, and compared its effects with those of ganciclovir (GCV).. BLCL were grown for 14 days in medium containing various doses of ACV or GCV, washed, irradiated, and tested for the presence of infectious virus in co-culture assays with cord blood mononuclear cells(CBMC) (21 CBMC to BLCL). B-cell transformation was assessed at 3-4 weeks of culture.. Both fresh and previously frozen BLCL released infectious virus, which transformed nearly all (92%) of CBMC co-cultures (n = 52). Transformation was not prevented by treatment with 100 microM ACV (88%, n = 52). Increasing the ACV dose to 200 microM (or 50 microg/mL) still allowed transformation in 4/9 (44%) cultures, while this and higher doses severely reduced the proliferation rate of the BLCL during ACV exposure. Infectious virus release was detectable within 1 day of ACV removal and BLCL irradiation. In contrast, GCV was able to prevent infectious virus release in 12/12 co-cultures at a concentration (15 microM) that only modestly reduced BLCL growth.. These results indicate that GCV is more effective at preventing release of infectious EBV from irradiated BLCL than ACV at concentrations that do not severely inhibit B-cell growth.

Topics: Acyclovir; Antigens, CD20; B-Lymphocytes; CD3 Complex; CD56 Antigen; Cell Division; Cell Line, Transformed; Cell Transformation, Viral; Coculture Techniques; Cytomegalovirus; Cytotoxicity Tests, Immunologic; Dose-Response Relationship, Drug; Fetal Blood; Fibroblasts; Flow Cytometry; Freezing; Ganciclovir; Herpesvirus 4, Human; HLA-DR Antigens; Humans; Immunoglobulin G; Kinetics; Leukocyte Common Antigens; Leukocytes, Mononuclear; T-Lymphocytes, Cytotoxic; Viral Load; Viral Plaque Assay

Greater than 90% of the human population acquire Epstein-Barr virus (EBV) in infancy and retain a lifelong latent infection without any clinical consequences. Nevertheless EBV has been identified as the causal agent of infectious mononucleosis, and is associated with several tumours including endemic Burkitt's lymphoma and B cell lymphomas in immunosupressed patients. B cells infected with EBV are transformed in vitro and grow continuously as lymphoblastoid cell lines. The growth of EBV-transformed B cells in vivo is controlled by the immune system. Studies on immunity to EBV have mainly focused on MHC class I-restricted CD8+ cytotoxic T cells specific for viral latent antigens. Here it is reported that in vitro stimulation of peripheral blood lymphocytes by autologous EBV-infected B cells, which have been induced to express lytic cycle antigens, gives rise to a predominantly CD4+ T cell response. Furthermore, the growth of EBV-infected B cells can also be regulated by these activated CD4+ T cells through apoptosis mediated by CD95-CD95 ligand (CD95L). CD95-CD95L-mediated apoptosis is an important mechanism of normal B cell growth regulation. As EBV-transformed B cells remain susceptible to this mechanism, the control of EBV in vivo may be not only by virus-specific CD8+ cytotoxic T cell immunity but also by normal mechanisms of immune regulation of B cell growth.

Topics: Acyclovir; Antibodies, Monoclonal; Antigens, Viral; Antiviral Agents; Apoptosis; B-Lymphocytes; CD4-Positive T-Lymphocytes; Cell Line; Cell Line, Transformed; Cell Transformation, Viral; Cytotoxicity, Immunologic; Fas Ligand Protein; fas Receptor; Flow Cytometry; Herpesvirus 4, Human; Humans; Jurkat Cells; Lymphocyte Cooperation; Membrane Glycoproteins; Mitomycins; Tetradecanoylphorbol Acetate

Reaction of phosphoroorganic synthons with 8-azaadenine, 8-aza-2, 6-diaminopurine, and 8-azaguanine using cesium carbonate yielded regioisomeric 8-azapurine N7-, N8-, and N9-(2-(phosphonomethoxy)alkyl) derivatives. This reaction followed by deprotection afforded isomeric 2-(phosphonomethoxy)ethyl (PME), (S)-(3-hydroxy-2-(phosphonomethoxy)propyl) [(S)-HPMP], (S)-(3-flouro-2-(phosphonomethoxy)propyl) [(S)-FPMP], (S)-(2-(phosphonomethoxy)propyl) [(S)-PMP], and (R)-(2-(phosphonomethoxy)propyl) [(R)-PMP] derivatives. 13C NMR spectra were used for structural assignment of the regioisomers. None of the 8-isomers exhibited any antiviral activity against herpesviruses, Moloney murine sarcoma virus (MSV), and/or HIV. 9-(S)-HPMP-8-azaadenine (23) and PME-8-azaguanine (65) were active against HSV-1, HSV-2, and CMV at 0.2-7 micrograms/mL, VZV at 0.04-0.4 microgram/mL, and MSV (at 0.3-0.6 microgram/mL). PME-8-azaguanine (65) and (R)-PMP-8-azaguanine (71a) protected MT-4 and CEM cells against HIV-1- and HIV-2-induced cytopathicity at a concentration of approximately 2 micrograms/mL.

Topics: 3T3 Cells; Adenine; Animals; Antiviral Agents; Cell Transformation, Viral; Cytomegalovirus; Cytopathogenic Effect, Viral; Guanine; Herpesvirus 1, Human; Herpesvirus 2, Human; Herpesvirus 3, Human; HIV-1; HIV-2; Magnetic Resonance Spectroscopy; Mice; Mice, Inbred C3H; Molecular Structure; Purines; Sarcoma Viruses, Murine

The nucleoside analog acyclovir (9-[2-hydroxy-ethoxy)methyl]guanine or acycloguanosine; ACV) inhibited the in vitro transformation of NIH 3T3 cells by Abelson murine leukemia virus and the proliferation of abl- and bcr-abl-transformed hemopoietic murine cell lines. This effect is selective since ACV at the same concentration had no effect on the src and Ha-ras transformation of NIH 3T3 cells or on the proliferation of hemopoietic cells transformed by those oncogenes. The inhibitory effect on proliferation of abl-transformed cells correlated with the extent of ACV triphosphate formation and incorporation into cellular DNA that was greater than that in normal or other oncogene-transformed cells. The increased ACV triphosphate formation might be due to a higher level of 5'-nucleotidase, the enzyme responsible for trace levels of ACV phosphorylation in uninfected cells.

Topics: 3T3 Cells; Abelson murine leukemia virus; Acyclovir; Animals; Cell Division; Cell Transformation, Viral; DNA; Genes, abl; In Vitro Techniques; Mice; Phosphorylation; Phosphotransferases

Epstein-Barr virus (EBV) has potent cell-growth-transforming activity for human B lymphocytes in vitro, yet appears to persist in the circulating B-cell pool of virus carriers in vivo as a largely asymptomatic (i.e., non-growth-transforming) infection. The true nature of this infection, and the identity of the cells involved, remain to be determined. Studies of Lewin et al. (1987) have suggested (i) that the frequency of virus-infected cells in the circulating B-cell pool differs in different buoyant density fractions, being most abundant in the low-density population, and (ii) that rare virus-infected cells with the capacity for direct in vitro outgrowth to EBV-transformed cell lines are segregated within the high-density population. We have repeated this work using B-cell fractions from a much larger panel of asymptomatic virus carriers and find (i) that the incidence of virus-infected B cells is not significantly different between high- and low-density fractions, and (ii) that virus-infected cells from both fractions give rise to EBV-transformed cell lines in culture predominantly through a 2-step mechanism of virus replication and secondary infection rather than by direct outgrowth.

Topics: Acyclovir; Adult; B-Lymphocytes; Cell Division; Cell Separation; Cell Transformation, Viral; Centrifugation, Density Gradient; Herpesvirus 4, Human; Humans; Virus Replication

Human herpesvirus 6 (HHV-6) is a newly identified lymphotropic herpesvirus. We have analyzed viral and host DNA replication in peripheral blood lymphocytes infected in the absence of drugs or infected in the presence of phosphonoacetic acid (PAA) or acyclovir (ACV). The results revealed the following: (i) Infection with HHV-6 resulted in the shutoff of host DNA replication. (ii) PAA at concentrations of 100 and 300 micrograms/ml significantly reduced virus replication. The drug inhibited viral DNA replication, whereas host cell DNA replication was not affected. This strongly suggests that HHV-6 encodes a PAA sensitive viral DNA polymerase. (iii) ACV at 20 microM did not interfere with virus production and virus spread. ACV at 100 microM only partly interfered with virus replication, whereas at 400 microM the block was more complete. Viral DNA replication was not affected by ACV at 20 microM. However, approximately 60 and 85% inhibition in viral DNA replication was observed in the presence of 100 and 400 microM of ACV. (iv) Assays for viral thymidine kinase (TK) revealed no significant increase in TK activity, whereas increased TK activity was noted following infection of the same peripheral blood lymphocytes with herpes simplex virus. Thus, either HHV-6 does not encode a tk enzyme which can phosphorylate ACV or the inefficient block may reflect lower sensitivity of the HHV-6 DNA polymerase to the drug.

Topics: Acyclovir; Cell Transformation, Viral; Cells, Cultured; DNA; DNA Replication; DNA, Viral; Fluorescent Antibody Technique; Humans; Lymphocytes; Microscopy, Electron; Phosphonoacetic Acid; Simplexvirus; Thymidine Kinase

Proteins from herpes simplex virus (HSV)-infected cells were used to reconstitute DNA synthesis in vitro on a preformed replication fork. The preformed replication fork consisted of a nicked, double-stranded, circular DNA molecule with a 5' single-strand tail that was noncomplementary to the template. The products of DNA synthesis on this substrate were rolling-circle molecules, as demonstrated by electron microscopy and alkaline agarose gel electrophoresis. The tails contained double-stranded regions, indicating that both leading- and lagging-strand DNA syntheses occurred. Rolling-circle DNA replication was dependent upon HSV DNA polymerase and ATP and was stimulated by a crude fraction containing ICP8 (HSV DNA-binding protein). Similar protein fractions from mock-infected cells were unable to support rolling-circle DNA replication. This in vitro DNA replication system should prove useful in the identification and characterization of the enzymatic activities required at the HSV replication fork.

Topics: Acyclovir; Animals; Antiviral Agents; Cell Nucleus; Cell Transformation, Viral; DNA Replication; DNA-Directed DNA Polymerase; DNA, Viral; Kinetics; Microscopy, Electron; Oligonucleotide Probes; Simplexvirus; Vero Cells

This report describes the first of 2 investigations studying mechanisms of Epstein-Barr virus (EBV) persistence in the infected host; specifically, we wish to determine the extent to which virus carriage within the B-cell system is dependent upon continued replication of the virus in permissive oropharyngeal epithelium. Levels of EBV infection at these 2 sites have been monitored in 21 acute infectious mononucleosis (IM) patients before, during and after treatment with high doses of acyclovir (ACV). Twelve patients received oral ACV for 10 days and 9 patients received i.v. ACV for 5 days before the 10-day oral course; all were followed prospectively for 28 days. Infectious EBV, detectable at high initial levels in the patients' throat washings, disappeared almost completely during ACV treatment, then returned again to high levels post treatment. In contrast, levels of virus-infected B cells in the blood showed no reduction linked to the period of ACV treatment nor any increase with resumption of EBV shedding. During IM, therefore, maintenance of high levels of virus carriage within the B-cell pool is not dependent upon the continual recruitment of newly infected B cells. This might reflect an inability of the immune T-cell response in acute IM patients to prevent continued expansion of the existing EBV-infected B-cell pool. Alternatively, it raises the possibility that EBV carriage in B cells in vivo is maintained through a virus:cell interaction which is not sensitive to virus-specific T-cell surveillance.

Topics: Acyclovir; Adolescent; Adult; Antigens, Viral; Cell Transformation, Viral; Epstein-Barr Virus Nuclear Antigens; Female; Follow-Up Studies; Herpesvirus 4, Human; Humans; Infectious Mononucleosis; Male; Oropharynx; Prospective Studies

The ability of LM cells, thymidine kinase-deficient LM cells (LMTK-), and LMTK- cells transformed to the LMTK+ phenotype by herpes simplex virus type 1 genetic information (LH7 cells) to anabolize the acyclovir congener ganciclovir was examined. About 50-fold more ganciclovir triphosphate was produced by LH7 cells than by either LM or LMTK- cells. Growth inhibition studies indicated that 180 and 120 microM ganciclovir were required to achieve 50% growth inhibition of LM and LMTK- cells, respectively; only 0.07 microM ganciclovir was necessary to achieve 50% inhibition of LH7 cells. DNA synthesis in the transformed cells was significantly reduced by ganciclovir treatment, whereas ganciclovir had little effect on DNA synthesis in the nontransformed cells. Alkaline sucrose gradient sedimentation analysis of transformed cellular DNA indicated that LH7 DNA synthesized in the presence of ganciclovir chased into mature DNA. Both LM and LH7 DNA synthesized in the presence of ganciclovir exhibited a concentration-dependent reduction in the rate of elongation into mature DNA. Finally, [14C]ganciclovir was incorporated internally into the growing chains of LH7 cells.

Topics: Acyclovir; Animals; Antiviral Agents; Cell Division; Cell Transformation, Viral; Chromatography, High Pressure Liquid; DNA, Viral; Ganciclovir; L Cells; Mice; Peptide Chain Elongation, Translational; Simplexvirus; Transfection; Transformation, Genetic

To establish cell systems appropriate for investigating the mode of action of antiherpetic nucleoside analogues, mutant cell strains were constructed from murine mammary carcinoma FM3A cells, which were deficient in TK, but were transformed with a recombinant plasmid DNA containing the HSV-2 TK gene. The transformed cells incorporated the viral DNA, expressed viral TK activity and showed unusually high sensitivity to the cytostatic action of the antiherpetic nucleoside analogues ACV and IVDU, both of which were only weakly inhibitory to the growth of the parent cells. Curiously, the FM3A cell strains transformed with HSV-2 TK gene showed a higher sensitivity to ACV and IVDU than the previously established cell line transformed with HSV-1 TK gene. This contrasts with the inhibitory effects of ACV and IVDU on acute HSV infection, since HSV-2 infection is slightly or considerably less susceptible than HSV-1 infection to inhibition by ACV or IVDU, respectively.

Topics: Acyclovir; Animals; Cell Line; Cell Transformation, Viral; Cloning, Molecular; Genes, Viral; Idoxuridine; Mammary Neoplasms, Experimental; Mice; Mutation; Simplexvirus; Thymidine Kinase

Epstein-Barr virus transformed human lymphocytes despite the presence of up to 500 microM acyclovir [9-(2-hydroxyethoxymethyl)guanine], a viral DNA polymerase inhibitor. The transformed cells contained multiple Epstein-Barr virus genome copy numbers. Functional viral DNA polymerase is probably not required for cell transformation and the initial amplification of the viral genome.

Topics: Acyclovir; B-Lymphocytes; Cell Transformation, Viral; DNA, Viral; Female; Genes, Viral; Herpesvirus 4, Human; Humans; Kinetics; Nucleic Acid Synthesis Inhibitors; Pregnancy; Umbilical Cord

As part of our study of antiherpetic acyclonucleosides, we synthesized a cyclic GMP analog, 9-[(2-hydroxy-1,3,2-dioxaphosphorinan-5-yl)oxymethyl]guanine P-oxide, sodium salt (2'-nor-cGMP), and discovered its potent and broad spectrum anti-DNA-viral activities. 2'-Nor-cGMP inhibits the replication of many DNA viruses, including herpes simplex virus, human cytomegalovirus, vaccinia, SV40, and adenovirus, but does not inhibit RNA viruses. In plaque reduction studies this potent antiviral agent is also approximately 10-fold more potent than 9-(1,3-dihydroxy-2-propoxymethyl)guanine (2'NDG) against varicella-zoster virus and inhibits cell transformation by bovine papilloma virus. Unlike 2'NDG, the potent activity of 2'-nor-cGMP against herpes virus is not dependent upon the action of virus-specified thymidine kinase. Intercellular metabolism of 2'-nor-cGMP produced small amounts of 2'NDG triphosphate which were insufficient to account for the antiviral activity observed, implying that this potent anti-DNA-viral agent operates by a mechanism different from that of known acyclonucleosides.

Topics: Acyclovir; Animals; Antiviral Agents; Cell Transformation, Viral; Cyclic GMP; DNA Viruses; Female; Ganciclovir; Guanine; Herpes Genitalis; Herpesvirus 3, Human; Male; Mice; Mice, Inbred ICR; Organophosphorus Compounds; Simplexvirus; Thymidine Kinase; Virus Replication

A murine cell line transformed with HSV TK (LH-1) exhibits a greatly enhanced cytotoxicity to the nucleoside analog 9-[(2-hydroxy-1-(hydroxymethyl)ethoxy) methyl]guanine (2'-NDG) as compared to the parental LM cell line (I50 LH-1 = 0.4 microM; I50 LM = 44.4 microM). Toxicity of 2'-NDG for LH-1 and LM is reversed only by the addition of 100 microM thymidine (dThd), indicating that 2'-NDG is a substrate for the viral and cellular TK. In LM(TK-) cells--murine cells expressing no TK activity, 2'-NDG cytotoxicity is partially reversed only with dGuo. A cyclic phosphate derivative of 2'-NDG, 2'-nor-cGMP, contains a phosphodiester bond, is also taken up by cells, and does not depend on viral TK for activation. LH-1 cells and LM(TK-) cells are inhibited by similar concentrations of this analog (5.1 and 4.1 microM, respectively). In all three cell lines (LM, LH-1, LM(TK-], the toxicity of 2'-nor-cGMP is significantly reversed with dGuo or cyclic dGMP. This pattern of reversal differs significantly from that observed with 2'-NDG, suggesting that 2'-nor-cGMP is metabolized as a guanosine analog, similar to acyclovir, in LM and LM(TK-) cells. These results indicate that a cyclic monophosphate analog of 2'-NDG can be activated independently of viral TK expression and that cellular metabolic pathways resulting in elevated dGTP concentrations are important for reversal of toxicity induced by guanosine-like nucleoside analogs.

Topics: Acyclovir; Animals; Cell Division; Cell Line; Cell Survival; Cell Transformation, Viral; Cyclic GMP; Deoxycytidine; Deoxyguanosine; Ganciclovir; Guanine; Mice; Organophosphorus Compounds; Simplexvirus; Thymidine; Thymidine Kinase

Four patients with typical manifestations of herpes simplex encephalitis were treated with Aciclovir. Infection with herpes simplex virus was confirmed in three of the four cases. Complete cure was achieved in each of the patients despite severe initial disease patterns. In view of these results in the treatment of a disease that had so far been partly lethal or produced severely defective states, the specific use of Aciclovir is emphasised.

Topics: Acyclovir; Adult; Cell Transformation, Viral; Cerebrospinal Fluid; Electroencephalography; Encephalitis; Epilepsy, Tonic-Clonic; Female; Herpes Simplex; Humans; Male; Middle Aged; Status Epilepticus

Infection with herpes simplex viruses (HSV) lead to a significant increase of the simian virus 40 (SV40) DNA content in the SV40-transformed hamster cell lines CO631 and Elona. Analysis of this gene-amplifying activity revealed (i) that it cosedimented with infectious herpesvirions in sucrose density gradients, (ii) that it was abolished by anti-HSV antibodies or (iii) by antiviral drugs acting on the HSV-induced DNA polymerase; and analysis of temperature-sensitive mutants showed that this DNA polymerase was an essential component of HSV-induced, gene-amplifying activity in SV40-transformed hamster cells.

Topics: Acyclovir; Animals; Cell Line; Cell Transformation, Viral; Centrifugation, Density Gradient; Cricetinae; DNA-Directed DNA Polymerase; DNA, Viral; Foscarnet; Gene Amplification; Genes, Viral; Mutation; Phosphonoacetic Acid; Simian virus 40; Simplexvirus; Temperature; Tunicamycin; Virus Replication

The metabolism of 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG), one of the most promising new anti-herpes virus compounds, in HeLa cells infected with herpes simplex virus type 1 was compared with that in the uninfected HeLa cells. In the virus-infected cells, the uptake of DHPG was enhanced and the major metabolites were found to be the mono-, di-, and triphosphate derivatives. The formation of these metabolites was dependent on the extracellular concentration of DHPG (0.5 to 5.0 microM). Virus-induced thymidine kinase was capable of phosphorylating DHPG to its monophosphate which could be further phosphorylated to the di- and triphosphate derivatives by the host cellular enzymes. Incorporation of the DHPG into DNA was observed in virus-infected cells. In contrast with 9-(2-hydroxyethoxymethyl)guanine, DHPG seemed not to serve as a chain terminator, but to be incorporated internally into DNA strands.

Topics: Acyclovir; Antiviral Agents; Biological Transport; Cell Transformation, Viral; Chromatography, High Pressure Liquid; Ganciclovir; HeLa Cells; Humans; Kinetics; Simplexvirus; Tritium

Topics: Acyclovir; Animals; Cell Line; Cell Transformation, Viral; Cricetinae; Guanine; Humans; Mesocricetus; Mice; Purine Nucleotides; Simplexvirus; Virus Replication

Topics: Acyclovir; Animals; Cell Division; Cell Line; Cell Transformation, Viral; DNA; Guanine; Mice; Phosphorylation; Simplexvirus; Thymidine Kinase; Transfection

Topics: Acyclovir; Adenosine Diphosphate; Animals; Cell Transformation, Viral; Chlorocebus aethiops; Erythrocytes; Guanine; Guanosine Monophosphate; Guanylate Kinases; Haplorhini; Humans; Kidney; Kinetics; Nucleoside-Phosphate Kinase; Organophosphorus Compounds; Phosphorylation; Phosphotransferases; Simplexvirus

Vaccinia and pseudorabies viruses are resistant to ACV [Acyclovir or 9-(2-hydroxyethoxymethyl)guanine] in normal cells. However, both viruses are sensitive in thymidine kinase (TK)-transformed cells in which the resident HSV-specific TK is able to phosphorylate the drug. This demonstrates the sensitivity of these viruses to phosphorylated ACV and suggests a wider antiviral activity for the phosphorylated drug.

Topics: Acyclovir; Animals; Cell Line; Cell Transformation, Viral; Guanine; Herpesvirus 1, Suid; Mice; Phosphorylation; Thymidine Kinase; Vaccinia virus; Viral Plaque Assay

Topics: Acyclovir; Animals; Cell Line; Cell Transformation, Viral; Guanine; Haplorhini; Humans; Kinetics; Nucleic Acid Synthesis Inhibitors; Phosphorylation; Purine Nucleosides; Simplexvirus; Substrate Specificity; Thymidine Kinase