In vivo antiviral activity of novel human immunodeficiency virus type 1 nucleocapsid p7 zinc finger inhibitors in a transgenic murine model

AIDS Research and Human Retroviruses

Volumn 19, Issue 2, 2003, Pages 91-101

  Schito, Marco L ^a,b   Goel, Atul ^b,c   Song, Yongsheng ^d   Inman, John K ^a   Fattah, Rasem J ^a   Rice, William G ^d   Turpin, Jim A ^e,f   Sher, Alan ^a   Appella, Ettore ^b  

^a NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES   (United States)

^b NATIONAL CANCER INSTITUTE   (United States)

^c CENTRAL DRUG RESEARCH INSTITUTE   (India)

^d Achillon Pharmaceuticals   (United States)

^e SOUTHERN RESEARCH INSTITUTE   (United States)

^f TherImmune Research Corporation   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 MERCAPTOBENZAMIDE THIOESTER DERIVATIVE; ANTIRETROVIRUS AGENT; DIDANOSINE; GAG PROTEIN; INDINAVIR; KYNOSTATIN 272; NUCLEOCAPSID PROTEIN; PROTEIN NCP7; UNCLASSIFIED DRUG; ZIDOVUDINE; ZINC FINGER PROTEIN;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIVIRAL ACTIVITY; ARTICLE; CONTROLLED STUDY; DRUG EFFICACY; DRUG POTENCY; DRUG TARGETING; HUMAN IMMUNODEFICIENCY VIRUS 1; INFECTION CONTROL; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; SPLEEN CELL; TRANSGENIC MOUSE; VIRION; VIRUS NUCLEOCAPSID; VIRUS REPLICATION;

ANIMALS; ANTI-HIV AGENTS; BENZAMIDES; CAPSID; CAPSID PROTEINS; DISEASE MODELS, ANIMAL; ESTERS; GENE PRODUCTS, GAG; HIV INFECTIONS; HIV-1; HUMANS; MICE; MICROBIAL SENSITIVITY TESTS; PYRIDINIUM COMPOUNDS; SULFHYDRYL COMPOUNDS; VIRAL PROTEINS; ZINC FINGERS;

EID: 0345269262     PISSN: 08892229     EISSN: None     Source Type: Journal    
DOI: 10.1089/088922203762688595     Document Type: Article

References (39)

1. + T cell demographics and dynamics in lymphatic tissues. Annu Rev Immunol 1999;17:625-656.
2. Pierson T, McArthur J, and Siliciano RF: Reservoirs for HIV-1: Mechanisms for viral persistence in the presence of antiviral immune responses and antiretroviral therapy. Annu Rev Immunol 2000;18:665-708.
3. 2+-dependent DNA integration in vitro. J Virol 1997;71:6225-6229.
4. Darlix JL, Vincent A, Gabus C, de Rocquigny H, and Roques B: Trans-activation of the 5′ to 3′ viral DNA strand transfer by nucleocapsid protein during reverse transcription of HIV 1 RNA. C R Acad Sci III 1993;316:763-771.
5. Li X, Quan Y, Arts EJ, Li Z, Preston BD, de Rocquigny H, Roques BP, Darlix JL, Kleiman L, Parniak MA, and Wainberg MA: Human immunodeficiency virus type 1 nucleocapsid protein (NCp7) directs specific initiation of minus-strand DNA synthesis primed by human tRNA(Lys3) in vitro: Studies of viral RNA molecules mutated in regions that flank the primer binding site. J Virol 1996;70:4996-5004.
6. Zybarth G and Carter C: Domains upstream of the protease (PR) in human immunedeficiency virus type 1 Gag-Pol influence PR autoprocessing. J Virol 1995;69:3878-3884.
7. Summers MF, South TL, Kim B, and Hare DR: High-resolution structure of an HIV zinc fingerlike domain via a new NMR-based distance geometry approach. Biochemistry 1990;29:329-340.
8. Berthoux L, Pechoux C, Ottmann M, Morel G, and Darlix JL: Mutations in the N-terminal domain of human immunodeficiency virus type 1 nucleocapsid protein affect virion core structure and proviral DNA synthesis. J Virol 1997;71:6973-6981.
9. Ottmann M, Gahus C, and Darlix JL: The central globular domain of the nucleocapsid protein of human immunodeficiency virus type 1 is critical for virion structure and infectivity. J Virol 1995;69:1778-1784.
10. Rice WG, Schaeffer CA, Graham L, Bu M, McDougal JS, Orloff SL, Villinger F, Young M, Oroszlan S, Fesen MR, et al.: The site of antiviral action of 3-nitrosobenzamide on the infectivity process of human immunodeficiency virus in human lymphocytes. Proc Natl Acad Sci USA 1993;90:9721-9724.
11. Rice WG, Supko JG, Malspeis L, Buckheit RW Jr, Clanton D, Bu M, Graham L, Schaeffer CA, Turpin JA, Domagala J, et al.: Inhibitors of HIV nucleocapsid protein zinc fingers as candidates for the treatment of AIDS. Science 1995;270:1194-1197.
12. Rice WG, Turpin JA, Huang M, Clanton D, Buckheit RW Jr, Covell DG, Wallqvist A, McDonnell NB, DeGuzman RN, Summers MF, Zalkow L, Bader JP, Haugwitz RD, and Sausville EA: Azodicarbonamide inhibits HIV-1 replication by targeting the nucleocapsid protein. Nat Med 1997;3:341-345.
13. Turpin JA, Song Y, Inman JK, Huang M, Wallqvist A, Maynard A, Covell DG, Rice WG, and Appella E: Synthesis and biological properties of novel pyridinioalkanoyl thiolesters (PATE) as anti-HIV-1 agents that target the viral nucleocapsid protein zinc fingers. J Med Chem 1999;42:67-86.
14. Goebel FRAN, Hemmer R, Schmit JC, Bogner JR, de Clercq E, Witvrouw M, Pannecouque C, Valeyev R, Vandevelde M, Margery H, and Tassignon JP: Phase I/II dose escalation and randomized withdrawal study with add-on azodicarbonamide in patients failing on current antiretroviral therapy. AIDS 2001;15:33-45.
15. Tassignon J, Ismaili J, Le Moine A, Van Laethem F, Leo O, Vandevelde M, and Goldman M: Azodicarbonamide inhibits T-cell responses in vitro and in vivo. Nat Med 1999;5:947-950.
16. Tassignon J, Vandevelde M, and Goldman M: Azodicarbonamide as a new T cell immunosuppressant: Synergy with cyclosporin A. Clin Immunol 2001;100:24-30.
17. Song Y, Goel A, Basrur V, Roberts PEA, Mikovits JA, Inman JK, Turpin JA, Rice W, and Appella E: Synthesis and biological properties of amino acid amide ligand-based pyridinioalkanoyl thioesters as anti-HIV agents. Bioorg Med Chem 2002;10:1263-1273.
18. Basrur V, Song Y, Mazur SJ, Higashimoto Y, Turpin JA, Rice WG, Inman JK, and Apella E: Inactivation of HIV-1 nucleocapsid protein P7 by pyridinioalkanoyl thioesters: Characterization of reaction products and proposed mechanism of action. J Biol Chem 2000;275:14890-14897.
19. Gazzinelli RT, Sher A, Cheever A, Gerstberger S, Martin MA, and Dickie P: Infection of human immunodeficiency virus 1 transgenic mice with Toxoplasma gondii stimulates proviral transcription in macrophages in vivo. J Exp Med 1996;183:1645-1655.
20. Doherty TM, Chougnet C, Schito M, Patterson BK, Fox C, Shearer GM, Englund G, and Sher A: Infection of HIV-1 transgenic mice with Mycobacterium avium induces the expression of infectious virus selectively from a Mac-1-positive host cell population. J Immunol 1999;163:1506-1515.
21. Dickie P, Felser J, Eckhaus M, Bryant J, Silver J, Marinos N, and Notkins AL: HIV-associated nephropathy in transgenic mice expressing HIV-1 genes. Virology 1991;185:109-119.
22. Dickie P: Nef modulation of HIV type 1 gene expression and cytopathicity in tissues of HIV transgenic mice. AIDS Res Hum Retroviruses 2000;16:777-790.
23. Hanna Z, Kay DG, Cool M, Jothy S, Rebai N, and Jolicoeur P: Transgenic mice expressing human immunodeficiency virus type 1 in immune cells develop a severe AIDS-like disease. J Virol 1998;72:121-132.
24. Santoro TJ, Bryant JL, Pellicoro J, Klotman ME, Kopp JB, Bruggeman LA, Franks RR, Notkins AL, and Klotman PE: Growth failure and AIDS-like cachexia syndrome in HIV-1 transgenic mice. Virology 1994;201:147-151.
25. Schito ML, Kennedy PE, Kowal RP, Berger EA, and Sher A: A human immunodeficiency virus-transgenic mouse model for assessing interventions that block microbial-induced proviral expression. J Infect Dis 2001;183:1592-1600.
26. Chougnet C, Freitag C, Schito M, Thomas EK, Sher A, and Shearer GM: In vivo CD40-CD154 (CD40 ligand) interaction induces integrated HIV expression by APC in an HIV-1-transgenic mouse model. J Immunol 2001;166:3210-3217.
27. Freitag C, Chougnet C, Schito M, Near KA, Shearer GM, Li C, Langhorne J, and Sher A: Malaria infection induces virus expression in human immunodeficiency virus transgenic mice by CD4 T cell-dependent immune activation. J Infect Dis 2001;183:1260-1268.
28. Martin JC and Bandres JC: Cells of the monocyte-macrophage lineage and pathogenesis of HIV-1 infection. J Acquir Immune Defic Syndr 1999;22:413-429.
29. Dickie P, Gazzinelli R, and Chang LJ: Models of HIV type 1 proviral gene expression in wild-type HIV and MLV/HIV transgenic mice. AIDS Res Hum Retroviruses 1996;12:1103-1116.
30. Doherty TM and Sher A: IL-12 promotes drug-induced clearance of Mycobacterium avium infection in mice. J Immunol 1998;160:5428-5435.
31. Kimpton J and Emerman M: Detection of replication-competent and pseudotyped human immunodeficiency virus with a sensitive cell line on the basis of activation of an integrated β-galactosidase gene. J Virol 1992;66:2232-2239.
32. Buckheit RW Jr, Hollingshead MG, Germany-Decker J, White EL, McMahon JB, Allen LB, Ross LJ, Decker WD, Westbrook L, Shannon WM, et al.: Thiazalobenzimidazole: Biological and biochemical anti-retroviral activity of a new nonnucleoside reverse transcriptase inhibitor. Antiviral Res 1993;21:247-265.
33. Turpin JA, Terpening SJ, Schaeffer CA, Yu G, Glover CJ, Felsted RL, Sausville EA, and Rice WG: Inhibitors of human immunodeficiency virus type 1 zinc fingers prevent normal processing of Gag precursors and result in the release of noninfectious virus particles. J Virol 1996;70:6180-6189.
34. Ghosh AK, Pretzer E, Cho H, Hussain KA, and Duzgunes N: Antiviral activity of UIC-PI, a novel inhibitor of the human immunodeficiency virus type 1 protease. Antiviral Res 2002;54:29-36.
35. Speck RR, Flexner C, Tian CJ, and Yu XF: Comparison of human immunodeficiency virus type 1 Pr55(Gag) and Pr160(Gag-Pol) processing intermediates that accumulate in primary and transformed cells treated with peptidic and nonpeptidic protease inhibitors. Antimicrob Agents Chemother 2000;44:1397-1403.
36. Kageyama S, Mimoto T, Murakawa Y, Nomizu M, Ford H Jr, Shirasaka T, Gulnik S, Erickson J, Takada K, Hayashi H, et al.: In vitro anti-human immunodeficiency virus (HIV) activities of transition state mimetic HIV protease inhibitors containing allophenylnorstatine. Antimicrob Agents Chemother 1993;37:810-817.
37. Perno CF, Newcomb FM, Davis DA, Aquaro S, Humphrey RW, Calio R, and Yarchoan R: Relative potency of protease inhibitors in monocytes/macrophages acutely and chronically infected with human immunodeficiency virus. J Infect Dis 1998;178:413-422.
38. Belkaid Y, Butcher B, and Sacks DL: Analysis of cytokine production by inflammatory mouse macrophages at the single-cell level: Selective impairment of IL-12 induction in Leishmania-infected cells. Eur J Immunol 1998;28:1389-1400.
39. Turpin JA, Schaeffer CA, Terpening SJ, Graham L, Bu M, and Rice WG: Reverse transcription of human immunodeficiency virus type 1 is blocked by retroviral zinc finger inhibitors. Antiviral Chem Chemother 1997;8:60-66.