Study on the Apparent Resistant Strains of Herpes Simplex Virus Type 1 against 9-β-D-Arabinofuranosyladenine

TAKESHI YOSHIDA; TATSUO SUZUTANI; MASANOBU AZUMA

doi:10.1620/tjem.156.279

TAKESHI YOSHIDA, TATSUO SUZUTANI, MASANOBU AZUMA

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Keywords: herpes simplex virus type 1, anti-herpes compound, drug resistant strains, adenosine deaminase

JOURNAL FREE ACCESS

1988 Volume 156 Issue 3 Pages 279-290

DOI https://doi.org/10.1620/tjem.156.279

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Published: 1988 Received: July 18, 1988 Available on J-STAGE: August 31, 2006 Accepted: October 07, 1988 Advance online publication: - Revised: -
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Date of correction: August 31, 2006 Reason for correction: - Correction: ABSTRACT Details: Wrong : YOSHIDA, T., SUZUTANI, T. and AZUMA, M. Study on the Apparent Resistant Strains of Herpes Simplex Virus Type 1 against 9 β-D-Arabinofuranosyladenine. Tohoku J. exp. Med., 1988, 156 (3), 279-290 - The appearance of drug resistant strains of herpes simplex virus type 1 (HSV-1) against 9-β-D-arabinofuranosyladenine (araA), in comparison with 5-iodo-2'-deoxyuridine (IUdR) and 9-(2-hydroxyethoxymethyl)guanine (acycloguanosine, ACG), has been investigated in green monkey kidney cell cultures (Vero) and human embryo lung cell cultures (HEL). Growth curves of HSV-1 in Vero cells and HEL cells in the presence or absence of 20μg/ml of araA showed that not only the viruses produced by these cells in the presence of araA but also the viruses produced in the absence of ara A were resistant to the same concentration of araA. However, both viruses were unable to grow in the presence of a combination of 20μg/ml of araA and 3μg/ml of erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) which is an inhibitor of adenosine deaminase. On the other hand, the viruses produced only in the presence of IUdR or ACG were resistant to each drug. All virus clones obtained from five serial clonings in the presence of araA alone or araA and EHNA in combination were not resistant to araA. These results show that the strain of HSV-1 resistant to araA is an apparently resistant strain, and a truly resistant strain to araA may not be established as easily as the truly resistant strains to IUdR and ACG.
Right : The appearance of drug resistant strains of herpes simplex virus type 1 (HSV-1) against 9-β-D-arabinofuranosyladenine (araA), in comparison with 5-iodo-2'-deoxyuridine (IUdR) and 9-(2-hydroxyethoxymethyl)guanine (acycloguanosine, ACG), has been investigated in green monkey kidney cell cultures (Vero) and human embryo lung cell cultures (HEL). Growth curves of HSV-1 in Vero cells and HEL cells in the presence or absence of 20 μg/ml of araA showed that not only the viruses produced by these cells in the presence of araA but also the viruses produced in the absence of araA were resistant to the same concentration of araA. However, both viruses were unable to grow in the presence of a combination of 20 μg/ml of araA and 3 μg/ml of erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) which is an inhibitor of adenosine deaminase. On the other hand, the viruses produced only in the presence of IUdR or ACG were resistant to each drug. All virus clones obtained from five serial clonings in the presence of araA alone or araA and EHNA in combination were not resistant to araA. These results show that the strain of HSV-1 resistant to araA is an apparently resistant strain, and a truly resistant strain to araA may not be established as easily as the truly resistant strains to IUdR and ACG.

Date of correction: August 31, 2006 Reason for correction: - Correction: CITATION Details: Wrong : 1) Agarwal, R.P. (1982) Inhibitors of adenosine deaminase. Pharmacol. Ther., 17, 399-429.
2) Chiou, H.C., Weller, S.K. & Coen, D.M. (1985) Mutations in the herpes simplex virus major DNA-binding protein gene leading to altered sensitivity to DNA polymerise inhibitors. Virology, 145, 213-226.
3) Coen, D.M., Furman, P.A., Gelep, P.T. & Schaffer, P.A. (1982) Mutations in the herpes simplex virus DNA polymerase genes can confer resistance to 9-β-D-arabinofuranosyladenine. J. Virol., 41, 909-918.
4) Coen, D.M., Aschman, D.P., Gelep, P.T., Retondo, M.J., Weller, S.K. & Schaffer, P.A. (1984) Fine mapping and molecular cloning of mutations in the herpes simplex virus DNA polymerase locus. J. Virol., 49, 236-247.
5) Coen, D.M., Fleming, H.E., Jr., Leslie, L.K. & Retondo, M.J. (1985) Sensitivity of arabinosyladenine-resistant mutants of herpes simplex virus to other antiviral drugs and mapping of drug hypersensitivity mutations to the DNA polymerase locus. J. Virol., 53, 477-488.
6) Crumpacker, C.S., Schnipper, L.E., Kowalsky, P.N. & Sherman, D.M. (1982) Resistance of herpes simplex virus to adenine arabinoside and E-5-(2-bromovinyl)-2'-deoxyuridine: A physical analysis. J. infect. Dis., 146, 167-172.
7) Darby, G., Field, H.J. & Salisbury, S.A. (1981) Altered substrate specificity of herpes simplex virus thymidine kinase confers acyclovir-resistance. Nature (Lond.), 289, 81-83.
8) De Clercq, E. (1984) Biochemical aspects of the selective antiherpes activity of nucleodside analogues. Biochem. Pharmacol., 33, 2159-2169.
9) De Clercq, E., Descamps, J., Verhelst, G., Walker, R.T., Jones, A.S., Torrence, P.F. & Shugar, D. (1980) Comparative efficacy of antiherpes drugs against different strains of herpes simplex virus. J. infect. Dis., 141, 563-574.
10) Fleming, H.E., Jr. & Coen, D.M. (1984) Herpes simplex virus mutants resistant to arabinosyladenine in the presence of deoxycoformycin. Antimicrob. Agents Chemother., 26, 382-387.
11) Gephart, J.F. & Lerner, A.M. (1981) Comparison of the effects of arabinosyladenine, arabinosylhypoxanthine, and arabinosyladenine-5'-monophosphate against herpes simplex virus, varicella-zoster virus, and cytomegalovirus with their effects on cellular deoxyribonucleic acid synthesis. Antimicrob. Agents Chemother., 19, 170-178.
12) Hirano, A., Yumura, K., Kurimura, T., Katsumoto, T., Moriyama, H. & Manabe, R. (1979) Analysis of herpes simplex virus isolated from patients with recurrent herpes keratitis exhibiting “treatment-resistance” to 5-iodo-2'-deoxyuridine. Acta vitrl., 23, 226-230.
13) Machida, H. (1986) Comparison of susceptibilities of varicella-zoster virus and herpes simplex viruses to nucleoside analogs. Antimicrob. Agents Chemother., 29, 524-526.
14) McLaren, C., Corey, L., Dekket, C. & Barry, D.W. (1983) In vitro sensitivity toacyclovir in genital herpes simplex viruses from acyclovir-treated patients. J. infect. Dis., 148, 868-875.
15) McLaren, C., Chen, M.S., Ghazzouli, I., Saral, R. & Burns, W.H. (1985) Drug resistance patterns of herpes simplex vius isolates from patients treated with acyclovir. Antimicrob. Agents Chemother., 28, 740-744.
16) North, T.W. & O'Connor, L. (1983) Effects of chirality in 9-(2-hydroxy-3-nonyl) adenine upon deoxyribonucleic acid synthesis in herpes simplex virus-infected cells. Biochem. Pharmacol., 32, 3541-3546.
17) Pelling, J.C., Drach, J.C. & Shipman, C., Jr. (1981) Internucleotide incorporation of arabinosyladenine into herpes simplex virus and mammalian cell DNA. Virology, 109, 323-335.
18) Plunkett, W. & Cohen, S.S. (1975) Two approaches that increase the activity of analogs of adenine nucleosides in animal cells. Cancer Res., 35, 1547-1554.
19) Plunkett, W. & Cohen, S.S. (1977) Increased toxicity of 9-β-v-arabinofuranosyladenine in the presence of an inhibitor of adenosine deaminase. Ann. N. Y. Acad. Sci., 284, 91-102.
20) Prusoff, W.H., Zucker, M., Mancini, W.R., Otto, M.J., Lin, T.S. & Lee, J.J. (1985) Basic biochemical and pharmacological aspects of antiviral agents. Antiviral Res. Suppl., 1, 1-10.
21) Prusoff, W.H., Lin, T.S. & Zucker, M. (1986) Potential targets for antiviral chemotherapy. Antiviral Res., 6, 311-328.
22) Schaeffer, H.J. & Schwender, C.F. (1974) Enzyme inhibitors. 26. Bridging hydrophobic and hydrophilic regions on adenosine deaminase with some 9-(2-hydroxy-3-alkyl)adenines. J. med. Chem., 17, 6-8.
23) Schwartz, P.M., Shipman, C., Jr. & Drach, J.C. (1976) Antiviral activity of arabinosyladenine and arabinosylhypoxanthine in herpes simplex virus-infected KB cells: selective inhibition of viral deoxyribonucleic acid synthesis in the presence of an adenosine deaminase inhibitor. Antimicrob. Agents Chemother., 10, 64-74.
24) Schwartz, P.M., Novack, J., Shipman, C., Jr. & Drach, J.C. (1984) Metabolism of arabinosyladenine in herpes simplex virus-infected and uninfected cells. Biochem. Phamacol., 33, 2431-2438.
25) Shannon, W.M., Arnett, G., Schabel, F.M., Jr., North, T.W. & Cohen, S.S. (1980) Erythro-9-(2-hydroxy-3-nonyl)adenine alone and in combination with 9-β-D-arabinofuranosyladenine in treatment of systemic herpesvirus infection in mice. Antimicrob. Agents Chemother., 18, 598-603.
26) Shewach, D.S. & Plunkett, W. (1986) Cellular retention of 9-β-D-arabinofuranosyladenine-5'-triphosphate and the pattern of recovery of DNA synthesis in chinese hamster ovary cells. Cancer Res., 46, 1581-1584.
27) Shipman, C., Jr., Smith, S.H., Carlson, R.H. & Drach, J.C. (1976) Antiviral activity of arabinosyladenine and arabinosylhypoxanthine in herpes simplex virus-infected KB cells: selective inhibition of viral deoxyribonucleic acid synthesis in synchronized suspension cultures. Antimicrob. Agents Chemother., 9, 120-127.
28) Smith, K.O., Kennell, W.L., Poirier, R.H. & Lynd, F.T. (1980) In vitro and in vivo resistance of herpes simplex virus to 9-(2-hydroxyethoxymethyl)guanine (acycloguanosine). Antimicrob. Agents Chemother., 17, 144-150.
29) Suzutani, T., Machida, H. & Sakuma, T. (1988a) Efficacies of antiherpes nucleosides against two strains of herpes simplex virus type 1 in Vero and human embryo lung fibroblast cells. Antimicrob. Agents Chemother., 32, 1046-1052.
30) Suzutani, T., Machida, H., Sakuma, T. & Azuma, M. (1988b) Effects of various nucleosides on antiviral activity and metabolism of 1-β-D-arabinofuranosyl-E-5-(2-bromovinyl) uracil against herpes simplex viruses type 1 and 2. Antimicrob. Agents. Chemother. in press.
31) Whitley, R.J., Soong, S.-J., Hirsch, M.S., Karchmer, A.W., Dolin, R., Galasso, G., Dunnick, J.K. & Alford, C.A. (1981) Herpes simplex encephalitis; Vidarabine therapy and diagnostic problems. New Engl. J. Med., 304, 313-318.

Right : 1) Agarwal, R. P. (1982) Inhibitors of adenosine deaminase. Pharmacol. Ther., 17, 399-429.
2) Chiou, H. C., Weller, S. K. & Coen, D. M. (1985) Mutations in the herpes simplex virus major DNA-binding protein gene leading to altered sensitivity to DNA polymerise inhibitors. Virology, 145, 213-226.
3) Coen, D. M., Furman, P. A., Gelep, P. T. & Schaffer, P. A. (1982) Mutations in the herpes simplex virus DNA polymerase genes can confer resistance to 9-β-D-arabinofuranosyladenine. J. Virol., 41, 909-918.
4) Coen, D. M., Aschman, D. P., Gelep, P. T., Retondo, M. J., Weller, S. K. & Schaffer, P. A. (1984) Fine mapping and molecular cloning of mutations in the herpes simplex virus DNA polymerase locus. J. Virol., 49, 236-247.
5) Coen, D. M., Fleming, H. E., Jr., Leslie, L. K. & Retondo, M. J. (1985) Sensitivity of arabinosyladenine-resistant mutants of herpes simplex virus to other antiviral drugs and mapping of drug hypersensitivity mutations to the DNA polymerase locus. J. Virol., 53, 477-488.
6) Crumpacker, C. S., Schnipper, L. E., Kowalsky, P. N. & Sherman, D. M. (1982) Resistance of herpes simplex virus to adenine arabinoside and E-5-(2-bromovinyl)-2'-deoxyuridine : A physical analysis. J. infect. Dis., 146, 167-172.
7) Darby, G., Field, H. J. & Salisbury, S. A. (1981) Altered substrate specificity of herpes simplex virus thymidine kinase confers acyclovir-resistance. Nature (Lond.), 289, 81-83.
8) De Clercq, E. (1984) Biochemical aspects of the selective antiherpes activity of nucleodside analogues. Biochem. Pharmacol., 33, 2159-2169.
9) De Clercq, E., Descamps, J., Verhelst, G., Walker, R. T., Jones, A. S., Torrence, P. F. & Shugar, D. (1980) Comparative efficacy of antiherpes drugs against different strains of herpes simplex virus. J. infect. Dis., 141, 563-574.
10) Fleming, H. E., Jr. & Coen, D. M. (1984) Herpes simplex virus mutants resistant to arabinosyladenine in the presence of deoxycoformycin. Antimicrob. Agents Chemother., 26, 382-387.
11) Gephart, J. F. & Lerner, A. M. (1981) Comparison of the effects of arabinosyladenine, arabinosylhypoxanthine, and arabinosyladenine-5'-monophosphate against herpes simplex virus, varicella-zoster virus, and cytomegalovirus with their effects on cellular deoxyribonucleic acid synthesis. Antimicrob. Agents Chemother., 19, 170-178.
12) Hirano, A., Yumura, K., Kurimura, T., Katsumoto, T., Moriyama, H. & Manabe, R. (1979) Analysis of herpes simplex virus isolated from patients with recurrent herpes keratitis exhibiting “treatment-resistance” to 5-iodo-2'-deoxyuridine. Acta virol., 23, 226-230.
13) Machida, H. (1986) Comparison of susceptibilities of varicella-zoster virus and herpes simplex viruses to nucleoside analogs. Antimicrob. Agents Chemother., 29, 524-526.
14) McLaren, C., Corey, L., Dekket, C. & Barry, D. W. (1983) In vitro sensitivity to acyclovir in genital herpes simplex viruses from acyclovir-treated patients. J. infect. Dis., 148, 868-875.
15) McLaren, C., Chen, M. S., Ghazzouli, I., Saral, R. & Burns, W. H. (1985) Drug resistance patterns of herpes simplex vius isolates from patients treated with acyclovir. Antimicrob. Agents Chemother., 28, 740-744.
16) North, T. W. & O'Connor, L. (1983) Effects of chirality in 9-(2-hydroxy-3-nonyl) adenine upon deoxyribonucleic acid synthesis in herpes simplex virus-infected cells. Biochem. Pharmacol., 32, 3541-3546.
17) Pelling, J. C., Drach, J. C. & Shipman, C., Jr. (1981) Internucleotide incorporation of arabinosyladenine into herpes simplex virus and mammalian cell DNA. Virology, 109, 323-335.
18) Plunkett, W. & Cohen, S. S. (1975) Two approaches that increase the activity of analogs of adenine nucleosides in animal cells. Cancer Res., 35, 1547-1554.
19) Plunkett, W. & Cohen, S. S. (1977) Increased toxicity of 9-β-D-arabinofuranosyladenine in the presence of an inhibitor of adenosine deaminase. Ann. N. Y. Acad. Sci., 284, 91-102.
20) Prusoff, W. H., Zucker, M., Mancini, W. R., Otto, M. J., Lin, T. S. & Lee, J. J. (1985) Basic biochemical and pharmacological aspects of antiviral agents. Antiviral Res. Suppl., 1, 1-10.
21) Prusoff, W. H., Lin, T. S. & Zucker, M. (1986) Potential targets for antiviral chemotherapy. Antiviral Res., 6, 311-328.
22) Schaeffer, H. J. & Schwender, C. F. (1974) Enzyme inhibitors. 26. Bridging hydrophobic and hydrophilic regions on adenosine deaminase with some 9-(2-hydroxy-3-alkyl)adenines. J. med. Chem., 17, 6-8.
23) Schwartz, P. M., Shipman, C., Jr. & Drach, J. C. (1976) Antiviral activity of arabinosyladenine and arabinosylhypoxanthine in herpes simplex virus-infected KB cells: selective inhibition of viral deoxyribonucleic acid synthesis in the presence of an adenosine deaminase inhibitor. Antimicrob. Agents Chemother., 10, 64-74.
24) Schwartz, P. M., Novack, J., Shipman, C., Jr. & Drach, J. C. (1984) Metabolism of arabinosyladenine in herpes simplex virus-infected and uninfected cells. Biochem. Phamacol., 33, 2431-2438.
25) Shannon, W. M., Arnett, G., Schabel, F. M., Jr., North, T. W. & Cohen, S. S. (1980) Erythro-9-(2-hydroxy-3-nonyl)adenine alone and in combination with 9-β-D-arabinofuranosyladenine in treatment of systemic herpesvirus infection in mice. Antimicrob. Agents Chemother., 18, 598-603.
26) Shewach, D. S. & Plunkett, W. (1986) Cellular retention of 9-β-D-arabinofuranosyladenine-5'-triphosphate and the pattern of recovery of DNA synthesis in chinese hamster ovary cells. Cancer Res., 46, 1581-1584.
27) Shipman, C., Jr., Smith, S. H., Carlson, R. H. & Drach, J. C. (1976) Antiviral activity of arabinosyladenine and arabinosylhypoxanthine in herpes simplex virus-infected KB cells: selective inhibition of viral deoxyribonucleic acid synthesis in synchronized suspension cultures. Antimicrob. Agents Chemother., 9, 120-127.
28) Smith, K. O., Kennell, W. L., Poirier, R. H. & Lynd, F. T. (1980) In vitro and in vivo resistance of herpes simplex virus to 9-(2-hydroxyethoxymethyl)guanine (acycloguanosine). Antimicrob. Agents Chemother., 17, 144-150.
29) Suzutani, T., Machida, H. & Sakuma, T. (1988a) Efficacies of antiherpes nucleosides against two strains of herpes simplex virus type 1 in Vero and human embryo lung fibroblast cells. Antimicrob. Agents Chemother., 32, 1046-1052.
30) Suzutani, T., Machida, H., Sakuma, T. & Azuma, M. (1988b) Effects of various nucleosides on antiviral activity and metabolism of 1-β-D-arabinofuranosyl-E-5-(2-bromovinyl) uracil against herpes simplex viruses type 1 and 2. Antimicrob. Agents. Chemother. in press.
31) Whitley, R. J., Soong, S. -J., Hirsch, M. S., Karchmer, A. W., Dolin, R., Galasso, G., Dunnick, J. K. & Alford, C. A. (1981) Herpes simplex encephalitis; Vidarabine therapy and diagnostic problems. New Engl. J. Med., 304, 313-318.

Date of correction: August 31, 2006 Reason for correction: - Correction: PDF FILE Details: -

Abstract

The appearance of drug resistant strains of herpes simplex virus type 1 (HSV-1) against 9-β-D-arabinofuranosyladenine (araA), in comparison with 5-iodo-2'-deoxyuridine (IUdR) and 9-(2-hydroxyethoxymethyl)guanine (acycloguanosine, ACG), has been investigated in green monkey kidney cell cultures (Vero) and human embryo lung cell cultures (HEL). Growth curves of HSV-1 in Vero cells and HEL cells in the presence or absence of 20 μg/ml of araA showed that not only the viruses produced by these cells in the presence of araA but also the viruses produced in the absence of araA were resistant to the same concentration of araA. However, both viruses were unable to grow in the presence of a combination of 20 μg/ml of araA and 3 μg/ml of erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) which is an inhibitor of adenosine deaminase. On the other hand, the viruses produced only in the presence of IUdR or ACG were resistant to each drug. All virus clones obtained from five serial clonings in the presence of araA alone or araA and EHNA in combination were not resistant to araA. These results show that the strain of HSV-1 resistant to araA is an apparently resistant strain, and a truly resistant strain to araA may not be established as easily as the truly resistant strains to IUdR and ACG.

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