Uncovering the complexities of retroviral ribonuclease H reveals its potential as a therapeutic target

AIDS Reviews

Volumn 4, Issue 4, 2002, Pages 183-194

  Klarmann, George J ^a   Hawkins, Mary E ^b   Le Grice, Stuart F J ^a  

^a NATIONAL CANCER INSTITUTE   (United States)

^b NATIONAL CANCER INSTITUTE   (United States)

Author keywords

Antiviral therapy; HIV; PPT; Reverse transcriptase; RNase H

Indexed keywords

ANTIRETROVIRUS AGENT; COUMARIN DERIVATIVE; DNA POLYMERASE; ILLIMAQUINONE; N (4 TERT BUTYLBENZOYL) 2 HYDROXY 1 NAPHTHALDEHYDE HYDRAZONE; NAPHTHOQUINONE; NOVOBIOCIN; NUCLEOSIDE ANALOG; PD 126338; PROTEINASE; PROTEINASE INHIBITOR; PURINE; RECOMBINANT ENZYME; RIBONUCLEASE H; RIBONUCLEASE H INHIBITOR; RNA DIRECTED DNA POLYMERASE; RNA DIRECTED DNA POLYMERASE INHIBITOR; TRANSFER RNA; UNCLASSIFIED DRUG; VIRUS DNA; ZIDOVUDINE 5' PHOSPHATE;

AMINO ACID SEQUENCE; ANTIVIRAL ACTIVITY; DNA CLEAVAGE; DNA INTEGRATION; DNA STRAND; DNA STRUCTURE; DNA SYNTHESIS; DRUG SCREENING; DRUG SPECIFICITY; DRUG STRUCTURE; DRUG TARGETING; ENZYME ACTIVITY; ENZYME INHIBITION; ENZYME PURIFICATION; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; HYDROLYSIS; IC 50; LONG TERM CARE; NONHUMAN; RETROPOSON; RETROVIRUS; REVIEW; RNA STRUCTURE; VIRUS INHIBITION; VIRUS MUTATION; VIRUS REPLICATION;

ANTI-HIV AGENTS; DRUG DELIVERY SYSTEMS; ENZYME INHIBITORS; HIV INFECTIONS; HIV-1; HIV-1 REVERSE TRANSCRIPTASE; HUMANS; RIBONUCLEASE H, CALF THYMUS; RNA;

EID: 0036822181     PISSN: 11396121     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (91)

1. Coffin J. Retroviridae and their replication. In: Virology. Strauss S (ed). New York: Lippincott-Raven Publishers 1996.
2. Arts E, Le Grice S. Interaction of retroviral reverse transcriptase with template-primer duplexes during replication. Prog Nucleic Acid Res Mol Biol 1998;58:339-93.
3. Emini E, Fan H. Immunological and pharacological approaches to the control of retroviral infections. In: Retroviruses. Coffin J, Hughes S, Varmus H (eds). Cold Spring Harbor, New York: Cold Spring Harbor Laboratory Press 1997:637-708.
4. Quiñones-Mateu M, Weber J, Rangel H, et al. HIV-1 fitness and antiviral drug resistance. AIDS Reviews 2001;3:223-42.
5. Scott W. The enzymatic basis for thymidine analogue resistance in HIV-1. AIDS Reviews 2001;3:194-200.
6. Le Grice S. Human immunodeficiency virus reverse transcriptase. In Reverse Transcriptase. Goff S, Skalka A (eds). Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press 1993:163-91.
7. Kohlstaedt L, Wang J, Rice P, et al. The structure of HIV-1 reverse transcriptase. In Reverse Transcriptase, Goff S, Skalka A. Cold Spring Harbor, NY, Cold Spring Harbor Laboratory Press, 1993;223-49.
8. Jacobo-Molina A, Ding J, Nanni R, et al. Crystal structure of human immunodeficiency virus type 1 reverse transcriptase complexed with double-stranded DNA at 3.0 Å resolution shows bent DNA. Proc Natl Acad Sci USA 1993;90:6320-4.
9. Huang H, Chopra R, Verdine G, et al. Structure of a covalently trapped catalytic complex of HIV 1 reverse transcriptase: Implications for drug resistance. Science 1998;282:1669-75.
10. Rodgers D, Gamblin S, Harris B, et al. The structure of unliganded reverse transcriptase from the human immunodeficiency virus type 1. Proc Natl Acad Sci USA 1995;92:1222-6.
11. Rausch J, Le Grice S. Reverse transcriptase-associated ribonuclease H activity as a target for antiviral chemotherapy. Antiv Chem Chemother 1997;8:173-85.
12. Miller J, Rausch J, Le Grice S. Evaluation of retroviral ribonuclease H activity. Methods Mol Biol 2001;160:335-54.
13. Telesnitsky A, Goff S. Reverse transcription and the generation of retroviral DNA. In: Retroviruses. Coffin J, Hughes S, Varmus, H (eds). Cold Spring Harbor, New York: Cold Spring Harbor Laboratory Press 1997;121-60.
14. Furfine E, Reardon J. Human immunodeficiency virus reverse transcriptase ribonuclease H: Specificity of tRNA(Lys3)-primer excision. Biochemistry 1991;30:7041-6.
15. Smith J, Roth M. Specificity of human immunodeficiency virus-1 reverse transcriptase associated ribonuclease H in removal of the minus-strand primer, tRNALys3. J Biol Chem 1992;267:15071-9.
16. Charneau P, Clavel F. A single-stranded gap in human immunodeficiency virus unintegrated linear DNA defined by a central copy of the polypurine tract. J Virol 1991;65:2415-21.
17. Charneau P, Alizon M, Clavel F. Second origin of DNA plus-strand synthesis is required for optimal human immunodeficiency virus replication. J Virol 1992;66:2814-20.
18. Harris J, Scott J, Traynor B, et al. Visna virus DNA: Discovery of a novel gapped structure. Virology 1981;113:573-83.
19. Heyman T, Agoutin B, Friant S, et al. Plus-strand DNA synthesis of the yeast retrotransposon Ty1 is initiated at two sites, PPT1 next to the 3′ LTR and PPT2 within the pol gene. PPT1 is sufficient for Ty1 transposition. J Mol Biol 1995;253:291-303.
20. Hungnes O, Tjotta E, Grinde B. The plus strand is discontinuous in a subpopulation of unintegrated HIV-1 DNA. Arch Virol 1991;116:133-41.
21. Kupiec J, Tobaly-Tapiero J, Canivet M, et al. Evidence for a gapped linear duplex DNA intermediate in the replicative cycle of human and simian spumaviruses. Nucleic Acids Res 1988;16:9557-65.
22. Schweizer M, Renne R, Neumann-Haefelin D. Structural analysis of proviral DNA in simian foamy virus (LK-3)-infected cells. Arch Virol 1989;109:103-14.
23. Klarmann G, Yu H, Chen X, Dougherty J, Preston B. Discontinuous plus strand DNA synthesis in human immunodeficiency virus type 1 infected cells and in a partially reconstituted cell free system. J Virol 1997;71:9259-69.
24. Miller M, Wang B, Bushman F. Human immunodeficiency virus type 1 preintegration complexes containing discontinuous plus strands are competent to integrate in vitro. J Virol 1995;69:3938-44.
25. Boone L, Skalka A. Viral DNA synthesized by avian retrovirus particles permeabilized with melittin. I. Kinetics of synthesis and size of minus- and plus-strand transcripts. J Virol 1981;37:109-16.
26. Wu T, Guo J, Bess J, Henderson L, Vevin J. Molecular requirements for human immunodeficiency virus type 1 plus-strand transfer: Analysis in reconstituted and endogenous reverse transcription systems. J Virol 1999;73:4794-805.
27. Smith C, Leon O, Smith J, Roth M. Sequence requirements for removal of tRNA by an isolated human immunodeficiency virus type 1 RNase H domain. J Virol 1998;72:6805-12.
28. Davies J II, Hostomska Z, Hostomsky Z, Jordan S, Mathews D. Crystal structure of the ribonuclease H domain of HIV-1 reverse transcriptase. Science 1991;252:88-95.
29. Ding J, Hughes S, Arnold E, Protein-nucleic acid interactions and DNA conformation in a complex of human immunodeficiency virus type 1 reverse transcriptase with a double-stranded DNA template-primer. Biopolymers 1997;44:125-38.
30. Sarafianos S, Das K, Tantillo C, et al. Crystal structure of HIV-1 reverse transcriptase in complex with a polypurine tract RNA:DNA. EMBO J 2001;20:1449-61.
31. Goedken E, Macqusee S. Co-crystal of Escherichia coli RNase HI with Mn2+ ions reveals two divalent metals bound in the active site. J Biol Chem 2001;276:7266-71.
32. Katayanagi K, Miyagawa M, Matsushima M, et al. Structural details of ribonuclease H from Escherichia coli as refined to an atomic resolution. J Mol Biol 1992;223:1029-52.
33. Katayanagi K, Okumura M, Morikawa K. Crystal structure of Escherichia coli ribonuclease HI in complex with Mg2+ at 2.8 Å resolution: Proof for a single Mg2+ binding site. Proteins: Struct Funct Genet 1993;17:337-46.
34. Yang W, Hendrickson W, Crouch R, Satow Y. Structure of ribonuclease H phased at 2 Å resolution by MAD analysis of the selenomethionyl protein. Science 1990;249:1398-405.
35. Schatz O, Cromme F, Gruninger-Leitch F, Le Grice S. Point mutations in conserved amino acid residues within the C-terminal domain of HIV-1 reverse transcriptase specifically repress RNase H function. FEBS Lett 1989;257:311-4.
36. Mizrahi V, Usdin M, Harington A, Dudding L. Site-directed mutagenesis of the conserved Asp-443 and Asp-498 carboxy-terminal residues of HIV-1 reverse transcriptase. Nucleic Acids Res 1990;18:5359-69.
37. Mizrahi V, Brooksbank R, Nkabinde N. Mutagenesis of the conserved aspartic acid 443, glutamic acid 478, asparagine 494, and aspartic acid 498 residues in the ribonuclease H domain of p66/p51 human immunodeficiency virus type I reverse transcriptase. Expression and biochemical analysis. J Biol Chem 1994;269:19245-9.
38. Julias J, Ferris A, Boyer P, Hughes S. Replication of phenotypically mixed human immunodeficiency virus type 1 virions containing catalytically active and catalytically inactive reverse transcriptase. J Virol 2001;75:6537-46.
39. Tisdale M, Schulze T, Larder B, Moelling K. Mutations within the RNase H domain of human immunodeficiency virus type 1 reverse transcriptase abolish virus infectivity. J Gen Virol 1991;72:59-66.
40. Haruki M, Tsunaka Y, Morikawa M, Iwai S, Kanaya S. Catalysis by Escherichia coli ribonuclease HI is facilitated by a phosphate group of the substrate. Biochemistry 2000;39:13939-44.
41. Keck J, Goedken E, Marqusee S. Activation/attenuation model for RNase H. A one-metal mechanism with second-metal inhibition. J Biol Chem 1998;273:34128-33.
42. Beese L, Steitz T. Structural basis for the 3′-5′ exonuclease activity of Escherichia coli DNA polymerase I: A two metal ion mechanism. EMBO J 1991;10:25-33.
43. Cirino N, Cameron C, Smith J, et al. Divalent cation modulation of the ribonuclease functions of human immunodeficiency virus reverse transcriptase. Biochemistry 1995;34:9936-43.
44. Blain S, Goff S. Differential effects of Moloney murine leukemia virus reverse transcriptase mutations on RNase H activity in Mg2+ and Mn2+. J Biol Chem 1996;271:1448-54.
45. Cowan J. Ohyama T, Howard K, Rausch J, Cowan S, Le Grice S. Metal-ion stoichiometry of the HIV-1 RT ribonuclease H domain: Evidence for two mutually exclusive sites leads to new mechanistic insights on metal-mediated hydrolysis in nucleic acid biochemistry. J Biol Inorg Chem 2000;5:67-74.
46. Peliska J, Benkovic S. Mechanism of DNA strand transfer reactions catalyzed by HIV-1 reverse transcriptase. Science 1992;258:1112-8.
47. Lener D, Budihas SR, Le Grice S. Mutating conserved residues in the ribonuclease H domain of Ty3 reverse transcriptase affects specialized cleavage events. J Biol Chem 2002;277:26486-95.
48. Prasad VR. Genetic analysis of retroviral reverse transcriptase. Structure and function. In: Reverse Transcriptase. Goff SP, Skalka AM (eds). Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press 1993.
49. Jacques P, Wohrl B, Howard K, Le Grice S. Modulation of HIV-1 reverse transcriptase function in "selectively deleted" p66/p51 heterodimers. J Biol Chem 1994;269:1388-93.
50. Cameron C, Ghosh M, Le Grice S, Benkovic S. Mutations in HIV reverse transcriptase which alter RNase H activity and decrease strand transfer efficiency are suppressed by HIV nucleocapsid protein. Proc Natl Acad Sci USA 1997;94:6700-5.
51. Ding J, Das K, Hsiou Y, et al. Structure and functional implications of the polymerase active site region in a complex of HIV-1 RT with a double-stranded DNA template- primer and an antibody Fab fragment at 2.8 A resolution. J Mol Biol 1998;284:1095-111.
52. Doublie S, Tabor S, Long A, Richardson C, Ellenberg T. Crystal structure of a bacteriophage T7 DNA replication complex at 2.2 Å resolution. Nature 1998;391:251-8.
53. Baillyo C, Crow S, Minnock A, Waring M. Demethylation of thymine residues affects DNA cleavage by endonucleases but not sequence recognition by drugs. J Mol Biol 1999;291:561-73.
54. Crothers D, Haran T, Nadeau J. Intrinsically bent DNA. J Biol Chem 1990;265:7093-6.
55. Dickerson R, Goodsell D, Kopka M. MPD and DNA bending in crystals and in solution. J Mol Biol 1996;256:108-25.
56. Fedoroff O, Salazar M, Reid B. Structure of a DNA:RNA hybrid duplex. Why RNase H does not cleave pure RNA. J Mol Biol 1993;233:509-23.
57. Hung S, Yu Q, Gray D, Ratliff R. Evidence from CD spectra that d(purine).r(pyrimidine) and r(purine).d(pyrimidine) hybrids are in different structural classes. Nucleic Acids Res 1994;22:4326-34.
58. Ratmeyer L, Vinayak R, Zhong Y, Zon G, Wilson W. Sequence specific thermodynamic and structural properties for DNA·RNA duplexes. Biochemistry 1994;33:5298-304.
59. Fedoroff O, Ge Y, Reid B. Solution structure of r(gaggacug):d(CAGTCCTC) hybrid: Implications for the initiation of HIV-1 (+)-strand synthesis. J Mol Biol 1997;269:225-39.
60. Kvaratskhelia M, Budihas S, Le Grice S. Pre-existing distortions in nucleic acid structure aid polypurine tract selection by HIV-1 reverse transcriptase. J Biol Chem 2002;277:16689-96.
61. Bebenek K, Beard W, Dardenn T, et al. A minor groove binding track in reverse transcriptase. Nat Struct Biol 1997;4:194-7.
62. Xiong Y, Eickbush T. Origin and evolution of retroelements based upon their reverse transcriptase sequences. EMBO J 1990;9:3353-62.
63. Gao H, Boyer P, Arnold E, Hughes S. Effects of mutations in the polymerase domain on the polymerase, RNase H and strand transfer activities of human immunodeficiency virus type 1 reverse transcriptase. J Mol Biol 1998;27:559-72.
64. Ghosh M, Jacques P, Rodgers D, Ottman M. Darlix J, Le Grice S. Alterations to the primer grip of p66 HIV-1 reverse transcriptase and their consequences for template-primer utilization. Biochemistry 1996;35:8553-62.
65. Jacques P, Wohrl B, Ottmann M, Darlix J, Le Grice S. Mutating the "primer grip" of p66 HIV-1 reverse transcriptase implicates tryptophan-229 in template-primer utilization. J Biol Chem 1994;269:26472-8.
66. Palaniappan C, Wisniewski M, Jacques P, Le Grice S, Fay P. Mutations within the primer grip region of HIV-1 reverse transcriptase result in loss of RNase H function. J Biol Chem 1997;272:11157-64.
67. Powell M, Ghosh M, Jacques P, Howard K, Le Grice S, Levin J. Alanine-scanning mutations in the "primer grip" of p66 HIV-1 reverse transcriptase result in selective loss of RNA priming activity. J Biol Chem 1997;272:13262-9.
68. Malik H, Eickbush T. Phylogenetic analysis of ribonuclease H domains suggests a late, chimeric origin of LTR retrotransposable elements and retroviruses. Genome Res 2001;11:1187-97.
69. Arion D, Sluis-Cremer N, Min K, Abram M, Fletcher R, Parniak M. Mutational analysis of Tyr-501 of HIV-1 reverse transcriptase. Effects on ribonuclease H activity and inhibition of this activity by N-acylhydrazones. J Biol Chem 2002;277:1370-4.
70. Julias J, McWilliams M, Sarafianos S, Arnold E, Hughes S. Mutations in the RNase H domain of HIV-1 reverse transcriptase affect the inhibition of DNA synthesis and the specificity of RNase H cleavage in vivo. Proc Natl Acad Sci USA 2002;99:9515-20.
71. Rausch J, Lener D, Miller J, Julias J, Hughes S, Le Grice S. Altering the RNase H primer grip of human immunodeficiency virus reverse transcriptase modifies cleavage specificity. Biochemistry 2002;41:4856-65.
72. Powell M, Beard W, Bebenek K, et al. Residues in the alphaH and alphaI helices of the HIV-1 reverse transcriptase thumb subdomain required for the specificity of RNase H-catalyzed removal of the polypurine tract primer. J Biol Chem 1999;274:19885-93.
73. Rausch J, Le Grice S. Substituting a conserved residue of the ribonuclease H domain alters substrte hydrolysis by retroviral reverse transcriptase. J Biol Chem 1997;272:8602-10.
74. Powell M, Levin J. Sequence and structural determinants required for priming of plus-strand DNA synthesis by the human immuno deficiency virus type 1 polypurine tract. J Virol 1996;70:5288-96.
75. Zhang W, Svarovskaia E, Barr R, Pathak V. Y586F mutation in murine leukemia virus reverse transcriptase decreases fidelity of DNA synthesis in regions associated with adeninethymine tracts. Proc Natl Acad Sci USA 2002;99:10090-5.
76. Schatz O, Cromme F, Naas T, et al. Inactivation of the RNaseH domain of HIV-1 reverse transcriptase blocks viral infectivity. In: Oncogenesis and AIDS. Papas T (ed). Houston, TX: Portfolio Publishing Company 1990:55-68.
77. Loya S, Tal R, Kashman Y, Hizi A. Illimaquinone, a selective inhibitor of the RNase H activity of human immunodeficiency virus type 1 reverse transcriptase. Antimicrob Agents Chemother 1990;34:2009-12.
78. Hafkemeyer P, Neftel K, Hobi R, et al. HP 0.35, a cephalosporin degradation product is a specific inhibitor of lentiviral RNAse H. Nucleic Acids Res 1991;19:4059-65.
79. Allen S, Krawczyk S, Mcgee L, Bischofberger N, Mulato A, Cherrington J. Inhibition of HIV-1 RNase H activity by nucleotide dimers. Antiviral Agents Chemother 1996;7:37-45.
80. Althaus I, Franks K, Langley K, et al. The amphiphilic properties of novenamines determine their activity as inhibitors of HIV-1 RNase H. Experienta 1996;52:329-35.
81. Tan C, Civil R, Mian A, So A, Downey K. Inhibition of the RNase H activity of HIV reverse transcriptase by azidothymidylate. Biochemistry 1991;30:4831-5.
82. Min B, Miyashiro H, Hattori M. Inhibitory effect of quinones on RNase H activity associated with HIV-1 reverse transcriptase. Phytother Res 2002;16:57-62.
83. Borkow G, Fletcher R, Barnard J, et al. Inhibition of the ribonuclease H and DNA polymerase activities of HIV-1 reverse transcriptase by N-(4-tert-butylbenzoyl)-2-hydroxy-1-naphthaldehyde hydrazone. Biochemistry 1997;36:3179-85.
84. Gabbara S, Davis W, Hupe L, Hupe D, Peliska J. Inhibitors of DNA strand transfer reactions catalyzed by HIV-1 reverse transcriptase. Biochemistry 1999;38:1370-6.
85. Hawkins M, Pfleiderer W, Mazumder A, Pommier Y, Balis F. Incorporation of a fluorescent guanosine analog into oligonucleotides and its application to a real assay for the HIV-1 integrase 3′-processing reaction. Nucleic Acids Res 1995;23:2872-80.
86. Driscoll S, Hawkins M, Balis F, Pffeiderer W, Laws W. Fluorescence properties of a new guanosine analog incorporated into small oligonucleotides. Biophys J 1997;73:3277-86.
87. Dyda F, Hickman A, Jenkins T, Engelman A, Craigie R, Davies D. Crystal structure of the catalytic domain of HIV-1 integrase: Similarity to other polynucleotidyl transferases. Science 1994;266:1981-6.
88. Zhao H, Neamati N, Hong H, et al. Coumarin-based inhibitors of HIV integrase. J Med Chem 1997;40:242-9.
89. Hazuda D, Felock P, Witmer M, et al. Inhibitors of strand transfer that prevent integration and inhibit HIV-1 replication in cells. Science 2000;287:646-50.
90. Wilhelm M, Boutabout M, Wilhelm F. Expression of an active form of recombinant Ty1 reverse transcriptase in Escherichia coli: A fusion protein containing the C-terminal region of the Ty1 integrase linked to the reverse transcriptase-RNase H domain exhibits polymerase and RNase H activities. Biochem J 2000;348:337-42.
91. Rausch J, Grice M, Henrietta M, Nymark M, Miller J, Le Grice S. Interaction of p55 reverse transcriptase from the Saccharomyces cerevisiae retrotransposon Ty3 with conformationally distinct nucleic acid duplexes. J Biol Chem 2000;275:13879-87.