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. 1997 Jul;71(7):5178–5188. doi: 10.1128/jvi.71.7.5178-5188.1997

Human immunodeficiency virus type 1 nucleocapsid protein promotes efficient strand transfer and specific viral DNA synthesis by inhibiting TAR-dependent self-priming from minus-strand strong-stop DNA.

J Guo 1, L E Henderson 1, J Bess 1, B Kane 1, J G Levin 1
PMCID: PMC191753  PMID: 9188585

Abstract

During the first strand transfer in reverse transcription, minus-strand strong-stop DNA [(-) SSDNA] is annealed to the 3' end of the acceptor RNA in a reaction mediated by base-pairing between terminal repeat sequences in the RNA and their complement in the DNA. The large stem-loop structure in the repeat region known as TAR could interfere with this annealing reaction. We have developed an in vitro human immunodeficiency virus type 1 (HIV-1) system to investigate the effect of TAR on strand transfer. Mutational analysis demonstrates that the presence of TAR in the donor and acceptor templates inhibits strand transfer and is correlated with extensive synthesis of heterogeneous DNAs formed by self-priming from (-) SSDNA. These DNAs are not precursors to the transfer product. Interestingly, products of self-priming are not detected in HIV-1 endogenous reactions; this suggests that virions contain a component which prevents self-priming. Our results show that the viral nucleocapsid protein (NC), which can destabilize secondary structures, drastically reduces self-priming and dramatically increases the efficiency of strand transfer. In addition, the data suggest that the ability to eliminate self-priming is a general property of NC which is manifested during reverse transcriptase pausing at sites of secondary structure in the template. We conclude that this activity of NC is critical for achieving highly efficient and specific viral DNA synthesis. Our findings raise the possibility that inactivation of NC could provide a new approach for targeting reverse transcription in anti-HIV therapy.

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Selected References

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  1. Adachi A., Gendelman H. E., Koenig S., Folks T., Willey R., Rabson A., Martin M. A. Production of acquired immunodeficiency syndrome-associated retrovirus in human and nonhuman cells transfected with an infectious molecular clone. J Virol. 1986 Aug;59(2):284–291. doi: 10.1128/jvi.59.2.284-291.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Aldovini A., Young R. A. Mutations of RNA and protein sequences involved in human immunodeficiency virus type 1 packaging result in production of noninfectious virus. J Virol. 1990 May;64(5):1920–1926. doi: 10.1128/jvi.64.5.1920-1926.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Allain B., Lapadat-Tapolsky M., Berlioz C., Darlix J. L. Transactivation of the minus-strand DNA transfer by nucleocapsid protein during reverse transcription of the retroviral genome. EMBO J. 1994 Feb 15;13(4):973–981. doi: 10.1002/j.1460-2075.1994.tb06342.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Arts E. J., Li X., Gu Z., Kleiman L., Parniak M. A., Wainberg M. A. Comparison of deoxyoligonucleotide and tRNA(Lys-3) as primers in an endogenous human immunodeficiency virus-1 in vitro reverse transcription/template-switching reaction. J Biol Chem. 1994 May 20;269(20):14672–14680. [PubMed] [Google Scholar]
  5. Arts E. J., Wainberg M. A. Human immunodeficiency virus type 1 reverse transcriptase and early events in reverse transcription. Adv Virus Res. 1996;46:97–163. doi: 10.1016/s0065-3527(08)60071-8. [DOI] [PubMed] [Google Scholar]
  6. Arts E.J., Li Z., Wainberg M.A. Analysis of Primer Extension and the First Template Switch during Human Immunodeficiency Virus Reverse Transcription. J Biomed Sci. 1995 Oct;2(4):314–321. doi: 10.1007/BF02255218. [DOI] [PubMed] [Google Scholar]
  7. Ben-Artzi H., Zeelon E., Amit B., Wortzel A., Gorecki M., Panet A. RNase H activity of reverse transcriptases on substrates derived from the 5' end of retroviral genome. J Biol Chem. 1993 Aug 5;268(22):16465–16471. [PubMed] [Google Scholar]
  8. Berkhout B., Jeang K. T. Detailed mutational analysis of TAR RNA: critical spacing between the bulge and loop recognition domains. Nucleic Acids Res. 1991 Nov 25;19(22):6169–6176. doi: 10.1093/nar/19.22.6169. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Bertrand E. L., Rossi J. J. Facilitation of hammerhead ribozyme catalysis by the nucleocapsid protein of HIV-1 and the heterogeneous nuclear ribonucleoprotein A1. EMBO J. 1994 Jun 15;13(12):2904–2912. doi: 10.1002/j.1460-2075.1994.tb06585.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. 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]
  11. Chen M., Garon C. F., Papas T. S. Native ribonucleoprotein is an efficient transcriptional complex of avian myeloblastosis virus. Proc Natl Acad Sci U S A. 1980 Mar;77(3):1296–1300. doi: 10.1073/pnas.77.3.1296. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Cirino N. M., Cameron C. E., Smith J. S., Rausch J. W., Roth M. J., Benkovic S. J., Le Grice S. F. Divalent cation modulation of the ribonuclease functions of human immunodeficiency virus reverse transcriptase. Biochemistry. 1995 Aug 8;34(31):9936–9943. doi: 10.1021/bi00031a016. [DOI] [PubMed] [Google Scholar]
  13. Collett M. S., Dierks P., Parsons J. T., Faras A. J. RNase H hydrolysis of the 5' terminus of the avian sarcoma virus genome during reverse transcription. Nature. 1978 Mar 9;272(5649):181–184. doi: 10.1038/272181a0. [DOI] [PubMed] [Google Scholar]
  14. Darlix J. L., Gabus C., Nugeyre M. T., Clavel F., Barré-Sinoussi F. Cis elements and trans-acting factors involved in the RNA dimerization of the human immunodeficiency virus HIV-1. J Mol Biol. 1990 Dec 5;216(3):689–699. doi: 10.1016/0022-2836(90)90392-Y. [DOI] [PubMed] [Google Scholar]
  15. Darlix J. L., Lapadat-Tapolsky M., de Rocquigny H., Roques B. P. First glimpses at structure-function relationships of the nucleocapsid protein of retroviruses. J Mol Biol. 1995 Dec 8;254(4):523–537. doi: 10.1006/jmbi.1995.0635. [DOI] [PubMed] [Google Scholar]
  16. De Rocquigny H., Gabus C., Vincent A., Fournié-Zaluski M. C., Roques B., Darlix J. L. Viral RNA annealing activities of human immunodeficiency virus type 1 nucleocapsid protein require only peptide domains outside the zinc fingers. Proc Natl Acad Sci U S A. 1992 Jul 15;89(14):6472–6476. doi: 10.1073/pnas.89.14.6472. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. DeStefano J. J., Buiser R. G., Mallaber L. M., Fay P. J., Bambara R. A. Parameters that influence processive synthesis and site-specific termination by human immunodeficiency virus reverse transcriptase on RNA and DNA templates. Biochim Biophys Acta. 1992 Jul 15;1131(3):270–280. doi: 10.1016/0167-4781(92)90025-u. [DOI] [PubMed] [Google Scholar]
  18. DeStefano J. J. Human immunodeficiency virus nucleocapsid protein stimulates strand transfer from internal regions of heteropolymeric RNA templates. Arch Virol. 1995;140(10):1775–1789. doi: 10.1007/BF01384341. [DOI] [PubMed] [Google Scholar]
  19. DeStefano J. J. Interaction of human immunodeficiency virus nucleocapsid protein with a structure mimicking a replication intermediate. Effects on stability, reverse transcriptase binding, and strand transfer. J Biol Chem. 1996 Jul 5;271(27):16350–16356. [PubMed] [Google Scholar]
  20. Dib-Hajj F., Khan R., Giedroc D. P. Retroviral nucleocapsid proteins possess potent nucleic acid strand renaturation activity. Protein Sci. 1993 Feb;2(2):231–243. doi: 10.1002/pro.5560020212. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Dorfman T., Luban J., Goff S. P., Haseltine W. A., Göttlinger H. G. Mapping of functionally important residues of a cysteine-histidine box in the human immunodeficiency virus type 1 nucleocapsid protein. J Virol. 1993 Oct;67(10):6159–6169. doi: 10.1128/jvi.67.10.6159-6169.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Feng Y. X., Copeland T. D., Henderson L. E., Gorelick R. J., Bosche W. J., Levin J. G., Rein A. HIV-1 nucleocapsid protein induces "maturation" of dimeric retroviral RNA in vitro. Proc Natl Acad Sci U S A. 1996 Jul 23;93(15):7577–7581. doi: 10.1073/pnas.93.15.7577. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Fleissner E., Tress E. Isolation of a ribonucleoprotein structure from oncornaviruses. J Virol. 1973 Dec;12(6):1612–1615. doi: 10.1128/jvi.12.6.1612-1615.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Fu T. B., Taylor J. When retroviral reverse transcriptases reach the end of their RNA templates. J Virol. 1992 Jul;66(7):4271–4278. doi: 10.1128/jvi.66.7.4271-4278.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Fu W., Gorelick R. J., Rein A. Characterization of human immunodeficiency virus type 1 dimeric RNA from wild-type and protease-defective virions. J Virol. 1994 Aug;68(8):5013–5018. doi: 10.1128/jvi.68.8.5013-5018.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Fu W., Rein A. Maturation of dimeric viral RNA of Moloney murine leukemia virus. J Virol. 1993 Sep;67(9):5443–5449. doi: 10.1128/jvi.67.9.5443-5449.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Furfine E. S., Reardon J. E. Reverse transcriptase.RNase H from the human immunodeficiency virus. Relationship of the DNA polymerase and RNA hydrolysis activities. J Biol Chem. 1991 Jan 5;266(1):406–412. [PubMed] [Google Scholar]
  28. Gilboa E., Mitra S. W., Goff S., Baltimore D. A detailed model of reverse transcription and tests of crucial aspects. Cell. 1979 Sep;18(1):93–100. doi: 10.1016/0092-8674(79)90357-x. [DOI] [PubMed] [Google Scholar]
  29. Gopalakrishnan V., Peliska J. A., Benkovic S. J. Human immunodeficiency virus type 1 reverse transcriptase: spatial and temporal relationship between the polymerase and RNase H activities. Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10763–10767. doi: 10.1073/pnas.89.22.10763. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Gorelick R. J., Chabot D. J., Ott D. E., Gagliardi T. D., Rein A., Henderson L. E., Arthur L. O. Genetic analysis of the zinc finger in the Moloney murine leukemia virus nucleocapsid domain: replacement of zinc-coordinating residues with other zinc-coordinating residues yields noninfectious particles containing genomic RNA. J Virol. 1996 Apr;70(4):2593–2597. doi: 10.1128/jvi.70.4.2593-2597.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. 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]
  32. Gorelick R. J., Henderson L. E., Hanser J. P., Rein A. Point mutants of Moloney murine leukemia virus that fail to package viral RNA: evidence for specific RNA recognition by a "zinc finger-like" protein sequence. Proc Natl Acad Sci U S A. 1988 Nov;85(22):8420–8424. doi: 10.1073/pnas.85.22.8420. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Gorelick R. J., Nigida S. M., Jr, Bess J. W., Jr, Arthur L. O., Henderson L. E., Rein A. Noninfectious human immunodeficiency virus type 1 mutants deficient in genomic RNA. J Virol. 1990 Jul;64(7):3207–3211. doi: 10.1128/jvi.64.7.3207-3211.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Guo J., Wu W., Yuan Z. Y., Post K., Crouch R. J., Levin J. G. Defects in primer-template binding, processive DNA synthesis, and RNase H activity associated with chimeric reverse transcriptases having the murine leukemia virus polymerase domain joined to Escherichia coli RNase H. Biochemistry. 1995 Apr 18;34(15):5018–5029. doi: 10.1021/bi00015a013. [DOI] [PubMed] [Google Scholar]
  35. Harrich D., Ulich C., Gaynor R. B. A critical role for the TAR element in promoting efficient human immunodeficiency virus type 1 reverse transcription. J Virol. 1996 Jun;70(6):4017–4027. doi: 10.1128/jvi.70.6.4017-4027.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Henderson L. E., Bowers M. A., Sowder R. C., 2nd, Serabyn S. A., Johnson D. G., Bess J. W., Jr, Arthur L. O., Bryant D. K., Fenselau C. Gag proteins of the highly replicative MN strain of human immunodeficiency virus type 1: posttranslational modifications, proteolytic processings, and complete amino acid sequences. J Virol. 1992 Apr;66(4):1856–1865. doi: 10.1128/jvi.66.4.1856-1865.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Herschlag D., Khosla M., Tsuchihashi Z., Karpel R. L. An RNA chaperone activity of non-specific RNA binding proteins in hammerhead ribozyme catalysis. EMBO J. 1994 Jun 15;13(12):2913–2924. doi: 10.1002/j.1460-2075.1994.tb06586.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Herschlag D. RNA chaperones and the RNA folding problem. J Biol Chem. 1995 Sep 8;270(36):20871–20874. doi: 10.1074/jbc.270.36.20871. [DOI] [PubMed] [Google Scholar]
  39. Hu W. S., Temin H. M. Retroviral recombination and reverse transcription. Science. 1990 Nov 30;250(4985):1227–1233. doi: 10.1126/science.1700865. [DOI] [PubMed] [Google Scholar]
  40. Ji X., Klarmann G. J., Preston B. D. Effect of human immunodeficiency virus type 1 (HIV-1) nucleocapsid protein on HIV-1 reverse transcriptase activity in vitro. Biochemistry. 1996 Jan 9;35(1):132–143. doi: 10.1021/bi951707e. [DOI] [PubMed] [Google Scholar]
  41. Karpel R. L., Henderson L. E., Oroszlan S. Interactions of retroviral structural proteins with single-stranded nucleic acids. J Biol Chem. 1987 Apr 15;262(11):4961–4967. [PubMed] [Google Scholar]
  42. Khan R., Giedroc D. P. Recombinant human immunodeficiency virus type 1 nucleocapsid (NCp7) protein unwinds tRNA. J Biol Chem. 1992 Apr 5;267(10):6689–6695. [PubMed] [Google Scholar]
  43. Klarmann G. J., Schauber C. A., Preston B. D. Template-directed pausing of DNA synthesis by HIV-1 reverse transcriptase during polymerization of HIV-1 sequences in vitro. J Biol Chem. 1993 May 5;268(13):9793–9802. [PubMed] [Google Scholar]
  44. Lapadat-Tapolsky M., De Rocquigny H., Van Gent D., Roques B., Plasterk R., Darlix J. L. Interactions between HIV-1 nucleocapsid protein and viral DNA may have important functions in the viral life cycle. Nucleic Acids Res. 1993 Feb 25;21(4):831–839. doi: 10.1093/nar/21.4.831. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Lapadat-Tapolsky M., Pernelle C., Borie C., Darlix J. L. Analysis of the nucleic acid annealing activities of nucleocapsid protein from HIV-1. Nucleic Acids Res. 1995 Jul 11;23(13):2434–2441. doi: 10.1093/nar/23.13.2434. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Li X., Quan Y., Arts E. J., Li Z., Preston B. D., de Rocquigny H., Roques B. P., Darlix J. L., Kleiman L., Parniak M. A. 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 Aug;70(8):4996–5004. doi: 10.1128/jvi.70.8.4996-5004.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Marquet R., Isel C., Ehresmann C., Ehresmann B. tRNAs as primer of reverse transcriptases. Biochimie. 1995;77(1-2):113–124. doi: 10.1016/0300-9084(96)88114-4. [DOI] [PubMed] [Google Scholar]
  48. Messer L. I., Currey K. M., O'Neill B. J., Maizel J. V., Jr, Levin J. G., Gerwin B. I. Functional analysis of reverse transcription by a frameshift pol mutant of murine leukemia virus. Virology. 1985 Oct 15;146(1):146–152. doi: 10.1016/0042-6822(85)90062-5. [DOI] [PubMed] [Google Scholar]
  49. Muesing M. A., Smith D. H., Capon D. J. Regulation of mRNA accumulation by a human immunodeficiency virus trans-activator protein. Cell. 1987 Feb 27;48(4):691–701. doi: 10.1016/0092-8674(87)90247-9. [DOI] [PubMed] [Google Scholar]
  50. Müller G., Strack B., Dannull J., Sproat B. S., Surovoy A., Jung G., Moelling K. Amino acid requirements of the nucleocapsid protein of HIV-1 for increasing catalytic activity of a Ki-ras ribozyme in vitro. J Mol Biol. 1994 Sep 30;242(4):422–429. doi: 10.1006/jmbi.1994.1592. [DOI] [PubMed] [Google Scholar]
  51. Panganiban A. T., Fiore D. Ordered interstrand and intrastrand DNA transfer during reverse transcription. Science. 1988 Aug 26;241(4869):1064–1069. doi: 10.1126/science.2457948. [DOI] [PubMed] [Google Scholar]
  52. Peliska J. A., Balasubramanian S., Giedroc D. P., Benkovic S. J. Recombinant HIV-1 nucleocapsid protein accelerates HIV-1 reverse transcriptase catalyzed DNA strand transfer reactions and modulates RNase H activity. Biochemistry. 1994 Nov 22;33(46):13817–13823. doi: 10.1021/bi00250a036. [DOI] [PubMed] [Google Scholar]
  53. Peliska J. A., Benkovic S. J. Mechanism of DNA strand transfer reactions catalyzed by HIV-1 reverse transcriptase. Science. 1992 Nov 13;258(5085):1112–1118. doi: 10.1126/science.1279806. [DOI] [PubMed] [Google Scholar]
  54. Post K., Guo J., Kalman E., Uchida T., Crouch R. J., Levin J. G. A large deletion in the connection subdomain of murine leukemia virus reverse transcriptase or replacement of the RNase H domain with Escherichia coli RNase H results in altered polymerase and RNase H activities. Biochemistry. 1993 Jun 1;32(21):5508–5517. doi: 10.1021/bi00072a004. [DOI] [PubMed] [Google Scholar]
  55. 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]
  56. Quan Y., Gu Z., Li X., Li Z., Morrow C. D., Wainberg M. A. Endogenous reverse transcription assays reveal high-level resistance to the triphosphate of (-)2'-dideoxy-3'-thiacytidine by mutated M184V human immunodeficiency virus type 1. J Virol. 1996 Aug;70(8):5642–5645. doi: 10.1128/jvi.70.8.5642-5645.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Rein A. Retroviral RNA packaging: a review. Arch Virol Suppl. 1994;9:513–522. doi: 10.1007/978-3-7091-9326-6_49. [DOI] [PubMed] [Google Scholar]
  58. Rice W. G., Supko J. G., Malspeis L., Buckheit R. W., Jr, Clanton D., Bu M., Graham L., Schaeffer C. A., Turpin J. A., Domagala J. Inhibitors of HIV nucleocapsid protein zinc fingers as candidates for the treatment of AIDS. Science. 1995 Nov 17;270(5239):1194–1197. doi: 10.1126/science.270.5239.1194. [DOI] [PubMed] [Google Scholar]
  59. Rodríguez-Rodríguez L., Tsuchihashi Z., Fuentes G. M., Bambara R. A., Fay P. J. Influence of human immunodeficiency virus nucleocapsid protein on synthesis and strand transfer by the reverse transcriptase in vitro. J Biol Chem. 1995 Jun 23;270(25):15005–15011. doi: 10.1074/jbc.270.25.15005. [DOI] [PubMed] [Google Scholar]
  60. Schatz O., Cromme F. V., Grüninger-Leitch F., Le Grice S. F. 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 Nov 6;257(2):311–314. doi: 10.1016/0014-5793(89)81559-5. [DOI] [PubMed] [Google Scholar]
  61. 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]
  62. Sykora K. W., Moelling K. Properties of the avian viral protein p12. J Gen Virol. 1981 Aug;55(Pt 2):379–391. doi: 10.1099/0022-1317-55-2-379. [DOI] [PubMed] [Google Scholar]
  63. Tanchou V., Gabus C., Rogemond V., Darlix J. L. Formation of stable and functional HIV-1 nucleoprotein complexes in vitro. J Mol Biol. 1995 Oct 6;252(5):563–571. doi: 10.1006/jmbi.1995.0520. [DOI] [PubMed] [Google Scholar]
  64. Tsuchihashi Z., Brown P. O. DNA strand exchange and selective DNA annealing promoted by the human immunodeficiency virus type 1 nucleocapsid protein. J Virol. 1994 Sep;68(9):5863–5870. doi: 10.1128/jvi.68.9.5863-5870.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  65. Tsuchihashi Z., Khosla M., Herschlag D. Protein enhancement of hammerhead ribozyme catalysis. Science. 1993 Oct 1;262(5130):99–102. doi: 10.1126/science.7692597. [DOI] [PubMed] [Google Scholar]
  66. Whitcomb J. M., Hughes S. H. Retroviral reverse transcription and integration: progress and problems. Annu Rev Cell Biol. 1992;8:275–306. doi: 10.1146/annurev.cb.08.110192.001423. [DOI] [PubMed] [Google Scholar]
  67. Wu W., Henderson L. E., Copeland T. D., Gorelick R. J., Bosche W. J., Rein A., Levin J. G. Human immunodeficiency virus type 1 nucleocapsid protein reduces reverse transcriptase pausing at a secondary structure near the murine leukemia virus polypurine tract. J Virol. 1996 Oct;70(10):7132–7142. doi: 10.1128/jvi.70.10.7132-7142.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. You J. C., McHenry C. S. HIV nucleocapsid protein. Expression in Escherichia coli, purification, and characterization. J Biol Chem. 1993 Aug 5;268(22):16519–16527. [PubMed] [Google Scholar]
  69. You J. C., McHenry C. S. Human immunodeficiency virus nucleocapsid protein accelerates strand transfer of the terminally redundant sequences involved in reverse transcription. J Biol Chem. 1994 Dec 16;269(50):31491–31495. [PubMed] [Google Scholar]
  70. Yu Q., Darlix J. L. The zinc finger of nucleocapsid protein of Friend murine leukemia virus is critical for proviral DNA synthesis in vivo. J Virol. 1996 Sep;70(9):5791–5798. doi: 10.1128/jvi.70.9.5791-5798.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]

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