Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1993 Oct 15;90(20):9721–9724. doi: 10.1073/pnas.90.20.9721

The site of antiviral action of 3-nitrosobenzamide on the infectivity process of human immunodeficiency virus in human lymphocytes.

W G Rice 1, C A Schaeffer 1, L Graham 1, M Bu 1, J S McDougal 1, S L Orloff 1, F Villinger 1, M Young 1, S Oroszlan 1, M R Fesen 1, et al.
PMCID: PMC47642  PMID: 7692451

Abstract

The C-nitroso compound 3-nitrosobenzamide, which has been shown to remove zinc from the retroviral-type zinc finger of p7NC nucleocapsid proteins, inhibits acute infection of human immunodeficiency virus type 1 in cultured human lymphocytes. The attachment of the virus to lymphocytes and the activities of critical viral enzymes, such as reverse transcriptase, protease, and integrase, are not affected by 3-nitrosobenzamide. However, the process of reverse transcription to form proviral DNA is effectively abolished by the drug, identifying the mode of action of 3-nitrosobenzamide as interrupting the role of p7NC in accurate proviral DNA synthesis during the infectious phase of the virus life cycle.

Full text

PDF
9721

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Berg J. M. Potential metal-binding domains in nucleic acid binding proteins. Science. 1986 Apr 25;232(4749):485–487. doi: 10.1126/science.2421409. [DOI] [PubMed] [Google Scholar]
  2. Bess J. W., Jr, Powell P. J., Issaq H. J., Schumack L. J., Grimes M. K., Henderson L. E., Arthur L. O. Tightly bound zinc in human immunodeficiency virus type 1, human T-cell leukemia virus type I, and other retroviruses. J Virol. 1992 Feb;66(2):840–847. doi: 10.1128/jvi.66.2.840-847.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bieth E., Gabus C., Darlix J. L. A study of the dimer formation of Rous sarcoma virus RNA and of its effect on viral protein synthesis in vitro. Nucleic Acids Res. 1990 Jan 11;18(1):119–127. doi: 10.1093/nar/18.1.119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Braun W., Vasák M., Robbins A. H., Stout C. D., Wagner G., Kägi J. H., Wüthrich K. Comparison of the NMR solution structure and the x-ray crystal structure of rat metallothionein-2. Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10124–10128. doi: 10.1073/pnas.89.21.10124. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Buki K. G., Bauer P. I., Mendeleyev J., Hakam A., Kun E. Destabilization of Zn2+ coordination in ADP-ribose transferase (polymerizing) by 6-nitroso-1,2-benzopyrone coincidental with inactivation of the polymerase but not the DNA binding function. FEBS Lett. 1991 Sep 23;290(1-2):181–185. doi: 10.1016/0014-5793(91)81255-7. [DOI] [PubMed] [Google Scholar]
  6. Cohen J. Early AZT takes a pounding in French-British 'Concorde' trial. Science. 1993 Apr 9;260(5105):157–157. doi: 10.1126/science.8469966. [DOI] [PubMed] [Google Scholar]
  7. Cornille F., Mely Y., Ficheux D., Savignol I., Gerard D., Darlix J. L., Fournie-Zaluski M. C., Roques B. P. Solid phase synthesis of the retroviral nucleocapsid protein NCp10 of Moloney murine leukaemia virus and related "zinc-fingers" in free SH forms. Influence of zinc chelation on structural and biochemical properties. Int J Pept Protein Res. 1990 Dec;36(6):551–558. [PubMed] [Google Scholar]
  8. Debouck C. The HIV-1 protease as a therapeutic target for AIDS. AIDS Res Hum Retroviruses. 1992 Feb;8(2):153–164. doi: 10.1089/aid.1992.8.153. [DOI] [PubMed] [Google Scholar]
  9. Eberle J., Seibl R. A new method for measuring reverse transcriptase activity by ELISA. J Virol Methods. 1992 Dec 1;40(3):347–356. doi: 10.1016/0166-0934(92)90092-r. [DOI] [PubMed] [Google Scholar]
  10. Erickson J., Neidhart D. J., VanDrie J., Kempf D. J., Wang X. C., Norbeck D. W., Plattner J. J., Rittenhouse J. W., Turon M., Wideburg N. Design, activity, and 2.8 A crystal structure of a C2 symmetric inhibitor complexed to HIV-1 protease. Science. 1990 Aug 3;249(4968):527–533. doi: 10.1126/science.2200122. [DOI] [PubMed] [Google Scholar]
  11. Fesen M. R., Kohn K. W., Leteurtre F., Pommier Y. Inhibitors of human immunodeficiency virus integrase. Proc Natl Acad Sci U S A. 1993 Mar 15;90(6):2399–2403. doi: 10.1073/pnas.90.6.2399. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gorelick R. J., Chabot D. J., Rein A., Henderson L. E., Arthur L. O. The two zinc fingers in the human immunodeficiency virus type 1 nucleocapsid protein are not functionally equivalent. J Virol. 1993 Jul;67(7):4027–4036. doi: 10.1128/jvi.67.7.4027-4036.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gradwohl G., Ménissier de Murcia J. M., Molinete M., Simonin F., Koken M., Hoeijmakers J. H., de Murcia G. The second zinc-finger domain of poly(ADP-ribose) polymerase determines specificity for single-stranded breaks in DNA. Proc Natl Acad Sci U S A. 1990 Apr;87(8):2990–2994. doi: 10.1073/pnas.87.8.2990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Gulakowski R. J., McMahon J. B., Staley P. G., Moran R. A., Boyd M. R. A semiautomated multiparameter approach for anti-HIV drug screening. J Virol Methods. 1991 Jun;33(1-2):87–100. doi: 10.1016/0166-0934(91)90010-w. [DOI] [PubMed] [Google Scholar]
  15. Hartman N. R., Johns D. G., Mitsuya H. Pharmacokinetic analysis of dextran sulfate in rats as pertains to its clinical usefulness for therapy of HIV infection. AIDS Res Hum Retroviruses. 1990 Jun;6(6):805–812. doi: 10.1089/aid.1990.6.805. [DOI] [PubMed] [Google Scholar]
  16. Jaxel C., Capranico G., Kerrigan D., Kohn K. W., Pommier Y. Effect of local DNA sequence on topoisomerase I cleavage in the presence or absence of camptothecin. J Biol Chem. 1991 Oct 25;266(30):20418–20423. [PubMed] [Google Scholar]
  17. Khan E., Mack J. P., Katz R. A., Kulkosky J., Skalka A. M. Retroviral integrase domains: DNA binding and the recognition of LTR sequences. Nucleic Acids Res. 1991 Feb 25;19(4):851–860. doi: 10.1093/nar/19.4.851. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Larder B. A., Darby G., Richman D. D. HIV with reduced sensitivity to zidovudine (AZT) isolated during prolonged therapy. Science. 1989 Mar 31;243(4899):1731–1734. doi: 10.1126/science.2467383. [DOI] [PubMed] [Google Scholar]
  19. Leteurtre F., Madalengoitia J., Orr A., Guzi T. J., Lehnert E., Macdonald T., Pommier Y., Cuzi T. J. Rational design and molecular effects of a new topoisomerase II inhibitor, azatoxin. Cancer Res. 1992 Aug 15;52(16):4478–4483. [PubMed] [Google Scholar]
  20. McDougal J. S., Mawle A., Cort S. P., Nicholson J. K., Cross G. D., Scheppler-Campbell J. A., Hicks D., Sligh J. Cellular tropism of the human retrovirus HTLV-III/LAV. I. Role of T cell activation and expression of the T4 antigen. J Immunol. 1985 Nov;135(5):3151–3162. [PubMed] [Google Scholar]
  21. Méric C., Goff S. P. Characterization of Moloney murine leukemia virus mutants with single-amino-acid substitutions in the Cys-His box of the nucleocapsid protein. J Virol. 1989 Apr;63(4):1558–1568. doi: 10.1128/jvi.63.4.1558-1568.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Nunberg J. H., Schleif W. A., Boots E. J., O'Brien J. A., Quintero J. C., Hoffman J. M., Emini E. A., Goldman M. E. Viral resistance to human immunodeficiency virus type 1-specific pyridinone reverse transcriptase inhibitors. J Virol. 1991 Sep;65(9):4887–4892. doi: 10.1128/jvi.65.9.4887-4892.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Prats A. C., Housset V., de Billy G., Cornille F., Prats H., Roques B., Darlix J. L. Viral RNA annealing activities of the nucleocapsid protein of Moloney murine leukemia virus are zinc independent. Nucleic Acids Res. 1991 Jul 11;19(13):3533–3541. doi: 10.1093/nar/19.13.3533. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Prats A. C., Sarih L., Gabus C., Litvak S., Keith G., Darlix J. L. Small finger protein of avian and murine retroviruses has nucleic acid annealing activity and positions the replication primer tRNA onto genomic RNA. EMBO J. 1988 Jun;7(6):1777–1783. doi: 10.1002/j.1460-2075.1988.tb03008.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Rajavashisth T. B., Taylor A. K., Andalibi A., Svenson K. L., Lusis A. J. Identification of a zinc finger protein that binds to the sterol regulatory element. Science. 1989 Aug 11;245(4918):640–643. doi: 10.1126/science.2562787. [DOI] [PubMed] [Google Scholar]
  26. Rice W. G., Hillyer C. D., Harten B., Schaeffer C. A., Dorminy M., Lackey D. A., 3rd, Kirsten E., Mendeleyev J., Buki K. G., Hakam A. Induction of endonuclease-mediated apoptosis in tumor cells by C-nitroso-substituted ligands of poly(ADP-ribose) polymerase. Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7703–7707. doi: 10.1073/pnas.89.16.7703. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Rice W. G., Schaeffer C. A., Harten B., Villinger F., South T. L., Summers M. F., Henderson L. E., Bess J. W., Jr, Arthur L. O., McDougal J. S. Inhibition of HIV-1 infectivity by zinc-ejecting aromatic C-nitroso compounds. Nature. 1993 Feb 4;361(6411):473–475. doi: 10.1038/361473a0. [DOI] [PubMed] [Google Scholar]
  28. Riehemann K., Sorg C. Sequence homologies between four cytoskeleton-associated proteins. Trends Biochem Sci. 1993 Mar;18(3):82–83. doi: 10.1016/0968-0004(93)90159-k. [DOI] [PubMed] [Google Scholar]
  29. South T. L., Blake P. R., Sowder R. C., 3rd, Arthur L. O., Henderson L. E., Summers M. F. The nucleocapsid protein isolated from HIV-1 particles binds zinc and forms retroviral-type zinc fingers. Biochemistry. 1990 Aug 28;29(34):7786–7789. doi: 10.1021/bi00486a002. [DOI] [PubMed] [Google Scholar]
  30. South T. L., Summers M. F. Zinc- and sequence-dependent binding to nucleic acids by the N-terminal zinc finger of the HIV-1 nucleocapsid protein: NMR structure of the complex with the Psi-site analog, dACGCC. Protein Sci. 1993 Jan;2(1):3–19. doi: 10.1002/pro.5560020102. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Summers M. F., Henderson L. E., Chance M. R., Bess J. W., Jr, South T. L., Blake P. R., Sagi I., Perez-Alvarado G., Sowder R. C., 3rd, Hare D. R. Nucleocapsid zinc fingers detected in retroviruses: EXAFS studies of intact viruses and the solution-state structure of the nucleocapsid protein from HIV-1. Protein Sci. 1992 May;1(5):563–574. doi: 10.1002/pro.5560010502. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Tse-Dinh Y. C., Beran-Steed R. K. Escherichia coli DNA topoisomerase I is a zinc metalloprotein with three repetitive zinc-binding domains. J Biol Chem. 1988 Nov 5;263(31):15857–15859. [PubMed] [Google Scholar]
  33. Vaishnav Y. N., Wong-Staal F. The biochemistry of AIDS. Annu Rev Biochem. 1991;60:577–630. doi: 10.1146/annurev.bi.60.070191.003045. [DOI] [PubMed] [Google Scholar]
  34. Wondrak E. M., Louis J. M., Mora P. T., Oroszlan S. Purification of HIV-1 wild-type protease and characterization of proteolytically inactive HIV-1 protease mutants by pepstatin A affinity chromatography. FEBS Lett. 1991 Mar 25;280(2):347–350. doi: 10.1016/0014-5793(91)80328-z. [DOI] [PubMed] [Google Scholar]
  35. Yong W. H., Wyman S., Levy J. A. Optimal conditions for synthesizing complementary DNA in the HIV-1 endogenous reverse transcriptase reaction. AIDS. 1990 Mar;4(3):199–206. doi: 10.1097/00002030-199003000-00004. [DOI] [PubMed] [Google Scholar]
  36. Zack J. A., Arrigo S. J., Weitsman S. R., Go A. S., Haislip A., Chen I. S. HIV-1 entry into quiescent primary lymphocytes: molecular analysis reveals a labile, latent viral structure. Cell. 1990 Apr 20;61(2):213–222. doi: 10.1016/0092-8674(90)90802-l. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES