Abstract
Human immunodeficiency virus (HIV) stores its genetic information in the form of RNA. This RNA genome is introduced into the target cell during infection. The virus belongs to the family of retroviruses, as it is able to reverse the normal flow of genetic information from DNA to RNA by copying its RNA genome into DNA using the viral enzyme reverse transcriptase (RT). Each viral particle contains two copies of positive-strand RNA genome enclosed by a core composed of 2,000 copies of the capsid (CA) protein. The RNA genome is tightly bound to nucleocapsid proteins (NC) and other enzymes needed for the early steps of viral infection and is protected by a capsid surrounded by a shell composed of matrix (MA) proteins. The shell is located underneath the virion envelope, a plasma membrane of host-cell origin. During infection, the viral envelope fuses with the cell membrane, releasing the capsid into the cytoplasm. Thereafter, the RNA genome undergoes a multistep process of conversion into DNA within the reverse transcription complex (RTC) (Fig. 2.1). After reverse transcription, the newly synthesized DNA is integrated into the host nuclear genome and permanently linked with their target cells.
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References
Aiyar A, Cobrinik D, Ge Z, Kung HJ, Leis J (1992) Interaction between retroviral U5 RNA and the T psi C loop of the tRNA(Trp) primer is required for efficient initiation of reverse transcription. J Virol 66(4):2464–2472
Arhel N (2010) Revisiting HIV-1 uncoating. Retrovirology 7:96
Arhel N, Munier S, Souque P, Mollier K, Charneau P (2006) Nuclear import defect of human immunodeficiency virus type 1 DNA flap mutants is not dependent on the viral strain or target cell type. J Virol 80(20):10262–10269
Arhel NJ, Souquere-Besse S, Munier S, Souque P, Guadagnini S, Rutherford S et al (2007) HIV-1 DNA Flap formation promotes uncoating of the pre-integration complex at the nuclear pore. EMBO J 26(12):3025–3037
Arnold E, Jacobo-Molina A, Nanni RG, Williams RL, Lu X, Ding J et al (1992) Structure of HIV-1 reverse transcriptase/DNA complex at 7 A resolution showing active site locations. Nature 357(6373):85–89
Arts EJ, Stetor SR, Li X, Rausch JW, Howard KJ, Ehresmann B et al (1996) Initiation of (−) strand DNA synthesis from tRNA(3Lys) on lentiviral RNAs: implications of specific HIV-1 RNA-tRNA(3Lys) interactions inhibiting primer utilization by retroviral reverse transcriptases. Proc Natl Acad Sci USA 93(19):10063–10068
Auxilien S, Keith G, Le Grice SF, Darlix JL (1999) Role of post-transcriptional modifications of primer tRNALys,3 in the fidelity and efficacy of plus strand DNA transfer during HIV-1 reverse transcription. J Biol Chem 274(7):4412–4420
Barraud P, Gaudin C, Dardel F, Tisne C (2007) New insights into the formation of HIV-1 reverse transcription initiation complex. Biochimie 89(10):1204–1210
Beerens N, Berkhout B (2002) Switching the in vitro tRNA usage of HIV-1 by simultaneous adaptation of the PBS and PAS. RNA 8(3):357–369
Beerens N, Kjems J (2010) Circularization of the HIV-1 genome facilitates strand transfer during reverse transcription. RNA 16(6):1226–1235
Beerens N, Groot F, Berkhout B (2001) Initiation of HIV-1 reverse transcription is regulated by a primer activation signal. J Biol Chem 276(33):31247–31256
Ben-Artzi H, Shemesh J, Zeelon E, Amit B, Kleiman L, Gorecki M et al (1996) Molecular analysis of the second template switch during reverse transcription of the HIV RNA template. Biochemistry 35(32):10549–10557
Benas P, Bec G, Keith G, Marquet R, Ehresmann C, Ehresmann B et al (2000) The crystal structure of HIV reverse-transcription primer tRNA(Lys,3) shows a canonical anticodon loop. RNA 6(10):1347–1355
Berkhout B, Schoneveld I (1993) Secondary structure of the HIV-2 leader RNA comprising the tRNA-primer binding site. Nucleic Acids Res 21(5):1171–1178
Berkhout B, van Wamel J, Klaver B (1995) Requirements for DNA strand transfer during reverse transcription in mutant HIV-1 virions. J Mol Biol 252(1):59–69
Berkhout B, Vastenhouw NL, Klasens BI, Huthoff H (2001) Structural features in the HIV-1 repeat region facilitate strand transfer during reverse transcription. RNA 7(8):1097–1114
Brule F, Bec G, Keith G, Le Grice SF, Roques BP, Ehresmann B et al (2000) In vitro evidence for the interaction of tRNA(3)(Lys) with U3 during the first strand transfer of HIV-1 reverse transcription. Nucleic Acids Res 28(2):634–640
Bukrinsky M (2004) A hard way to the nucleus. Mol Med 10(1–6):1–5
Bukrinsky MI, Sharova N, McDonald TL, Pushkarskaya T, Tarpley WG, Stevenson M (1993) Association of integrase, matrix, and reverse transcriptase antigens of human immunodeficiency virus type 1 with viral nucleic acids following acute infection. Proc Natl Acad Sci USA 90(13):6125–6129
Burnett BP, McHenry CS (1997) Posttranscriptional modification of retroviral primers is required for late stages of DNA replication. Proc Natl Acad Sci USA 94(14):7210–7215
Cen S, Khorchid A, Gabor J, Rong L, Wainberg MA, Kleiman L (2000) Roles of Pr55(gag) and NCp7 in tRNA(3)(Lys) genomic placement and the initiation step of reverse transcription in human immunodeficiency virus type 1. J Virol 74(22):10796–10800
Cen S, Khorchid A, Javanbakht H, Gabor J, Stello T, Shiba K et al (2001) Incorporation of lysyl-tRNA synthetase into human immunodeficiency virus type 1. J Virol 75(11):5043–5048
Cen S, Javanbakht H, Kim S, Shiba K, Craven R, Rein A et al (2002) Retrovirus-specific packaging of aminoacyl-tRNA synthetases with cognate primer tRNAs. J Virol 76(24):13111–13115
Cen S, Javanbakht H, Niu M, Kleiman L (2004) Ability of wild-type and mutant lysyl-tRNA synthetase to facilitate tRNA(Lys) incorporation into human immunodeficiency virus type 1. J Virol 78(3):1595–1601
Chan B, Weidemaier K, Yip WT, Barbara PF, Musier-Forsyth K (1999) Intra-tRNA distance measurements for nucleocapsid proteindependent tRNA unwinding during priming of HIV reverse transcription. Proc Natl Acad Sci USA 96(2):459–464
Charneau P, Alizon M, Clavel F (1992) A second origin of DNA plus-strand synthesis is required for optimal human immunodeficiency virus replication. J Virol 66(5):2814–2820
Charneau P, Mirambeau G, Roux P, Paulous S, Buc H, Clavel F (1994) HIV-1 reverse transcription. A termination step at the center of the genome. J Mol Biol 241(5):651–662
Chen H, Engelman A (2001) Asymmetric processing of human immunodeficiency virus type 1 cDNA in vivo: implications for functional end coupling during the chemical steps of DNA transposition. Mol Cell Biol 21(20):6758–6767
Chen Y, Balakrishnan M, Roques BP, Bambara RA (2003a) Steps of the acceptor invasion mechanism for HIV-1 minus strand strong stop transfer. J Biol Chem 278(40):38368–38375
Chen Y, Balakrishnan M, Roques BP, Fay PJ, Bambara RA (2003b) Mechanism of minus strand strong stop transfer in HIV-1 reverse transcription. J Biol Chem 278(10):8006–8017
Chun TW, Carruth L, Finzi D, Shen X, DiGiuseppe JA, Taylor H et al (1997) Quantification of latent tissue reservoirs and total body viral load in HIV-1 infection. Nature 387(6629): 183–188
Cobrinik D, Soskey L, Leis J (1988) A retroviral RNA secondary structure required for efficient initiation of reverse transcription. J Virol 62(10):3622–3630
Cobrinik D, Aiyar A, Ge Z, Katzman M, Huang H, Leis J (1991) Overlapping retrovirus U5 sequence elements are required for efficient integration and initiation of reverse transcription. J Virol 65(7):3864–3872
Coffin JM (1979) Structure, replication, and recombination of retrovirus genomes: some unifying hypotheses. J Gen Virol 42(1):1–26
Corver J, Lenches E, Smith K, Robison RA, Sando T, Strauss EG et al (2003) Fine mapping of a cis-acting sequence element in yellow fever virus RNA that is required for RNA replication and cyclization. J Virol 77(3):2265–2270
Cristofari G, Bampi C, Wilhelm M, Wilhelm FX, Darlix JL (2002) A 5′-3′ long-range interaction in Ty1 RNA controls its reverse transcription and retrotransposition. EMBO J 21(16):4368–4379
Das AT, Koken SE, Essink BB, van Wamel JL, Berkhout B (1994) Human immunodeficiency virus uses tRNA(Lys,3) as primer for reverse transcription in HeLa-CD4+ cells. FEBS Lett 341(1):49–53
Das AT, Klaver B, Berkhout B (1995) Reduced replication of human immunodeficiency virus type 1 mutants that use reverse transcription primers other than the natural tRNA(3Lys). J Virol 69(5):3090–3097
DeStefano JJ, Buiser RG, Mallaber LM, Myers TW, Bambara RA, Fay PJ (1991) Polymerization and RNase H activities of the reverse transcriptases from avian myeloblastosis, human immunodeficiency, and Moloney murine leukemia viruses are functionally uncoupled. J Biol Chem 266(12):7423–7431
DeStefano JJ, Bambara RA, Fay PJ (1993) Parameters that influence the binding of human immunodeficiency virus reverse transcriptase to nucleic acid structures. Biochemistry 32(27):6908–6915
Dina D, Benz EW Jr (1980) Structure of murine sarcoma virus DNA replicative intermediates synthesized in vitro. J Virol 33(1):377–389
Dvorin JD, Malim MH (2003) Intracellular trafficking of HIV-1 cores: journey to the center of the cell. Curr Top Microbiol Immunol 281:179–208
Egele C, Schaub E, Ramalanjaona N, Piemont E, Ficheux D, Roques B et al (2004) HIV-1 nucleocapsid protein binds to the viral DNA initiation sequences and chaperones their kissing interactions. J Mol Biol 342(2):453–466
Ellison V, Abrams H, Roe T, Lifson J, Brown P (1990) Human immunodeficiency virus integration in a cell-free system. J Virol 64(6):2711–2715
Engelman A, Mizuuchi K, Craigie R (1991) HIV-1 DNA integration: mechanism of viral DNA cleavage and DNA strand transfer. Cell 67(6):1211–1221
Farnet CM, Bushman FD (1997) HIV-1 cDNA integration: requirement of HMG I(Y) protein for function of preintegration complexes in vitro. Cell 88(4):483–492
Farnet CM, Haseltine WA (1991a) Circularization of human immunodeficiency virus type 1 DNA in vitro. J Virol 65(12):6942–6952
Farnet CM, Haseltine WA (1991b) Determination of viral proteins present in the human immunodeficiency virus type 1 preintegration complex. J Virol 65(4):1910–1915
Forshey BM, Aiken C (2003) Disassembly of human immunodeficiency virus type 1 cores in vitro reveals association of Nef with the subviral ribonucleoprotein complex. J Virol 77(7): 4409–4414
Forshey BM, von Schwedler U, Sundquist WI, Aiken C (2002) Formation of a human immunodeficiency virus type 1 core of optimal stability is crucial for viral replication. J Virol 76(11): 5667–5677
Freund F, Boulme F, Litvak S, Tarrago-Litvak L (2001) Initiation of HIV-2 reverse transcription: a secondary structure model of the RNA-tRNA(Lys3) duplex. Nucleic Acids Res 29(13): 2757–2765
Gabor J, Cen S, Javanbakht H, Niu M, Kleiman L (2002) Effect of altering the tRNA(Lys)(3) concentration in human immunodeficiency virus type 1 upon its annealing to viral RNA, GagPol incorporation, and viral infectivity. J Virol 76(18):9096–9102
Gabus C, Ficheux D, Rau M, Keith G, Sandmeyer S, Darlix JL (1998) The yeast Ty3 retrotransposon contains a 5′-3′ bipartite primer-binding site and encodes nucleocapsid protein NCp9 functionally homologous to HIV-1 NCp7. EMBO J 17(16):4873–4880
Gabus C, Ivanyi-Nagy R, Depollier J, Bucheton A, Pelisson A, Darlix JL (2006) Characterization of a nucleocapsid-like region and of two distinct primer tRNALys,2 binding sites in the endogenous retrovirus Gypsy. Nucleic Acids Res 34(20):5764–5777
Gallay P, Swingler S, Song J, Bushman F, Trono D (1995) HIV nuclear import is governed by the phosphotyrosine-mediated binding of matrix to the core domain of integrase. Cell 83(4):569–576
Ganser BK, Li S, Klishko VY, Finch JT, Sundquist WI (1999) Assembly and analysis of conical models for the HIV-1 core. Science 283(5398):80–83
Gilboa E, Goff S, Shields A, Yoshimura F, Mitra S, Baltimore D (1979a) In vitro synthesis of a 9 kbp terminally redundant DNA carrying the infectivity of Moloney murine leukemia virus. Cell 16(4):863–874
Gilboa E, Mitra SW, Goff S, Baltimore D (1979b) A detailed model of reverse transcription and tests of crucial aspects. Cell 18(1):93–100
Gilmartin GM, Fleming ES, Oetjen J, Graveley BR (1995) CPSF recognition of an HIV-1 mRNA 3′-processing enhancer: multiple sequence contacts involved in poly(A) site definition. Genes Dev 9(1):72–83
Goldschmidt V, Rigourd M, Ehresmann C, Le Grice SF, Ehresmann B, Marquet R (2002) Direct and indirect contributions of RNA secondary structure elements to the initiation of HIV-1 reverse transcription. J Biol Chem 277(45):43233–43242
Goldschmidt V, Paillart JC, Rigourd M, Ehresmann B, Aubertin AM, Ehresmann C et al (2004) Structural variability of the initiation complex of HIV-1 reverse transcription. J Biol Chem 279(34):35923–35931
Gopalakrishnan V, Peliska JA, Benkovic SJ (1992) Human immunodeficiency virus type 1 reverse transcriptase: spatial and temporal relationship between the polymerase and RNase H activities. Proc Natl Acad Sci USA 89(22):10763–10767
Guntaka RV (1993) Transcription termination and polyadenylation in retroviruses. Microbiol Rev 57(3):511–521
Guo J, Henderson LE, Bess J, Kane B, Levin JG (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 Virol 71(7):5178–5188
Guo F, Gabor J, Cen S, Hu K, Mouland AJ, Kleiman L (2005) Inhibition of cellular HIV-1 protease activity by lysyl-tRNA synthetase. J Biol Chem 280(28):26018–26023
Guo F, Saadatmand J, Niu M, Kleiman L (2009) Roles of Gag and NCp7 in facilitating tRNA(Lys)(3) Annealing to viral RNA in human immunodeficiency virus type 1. J Virol 83(16):8099–8107
Hahn CS, Hahn YS, Rice CM, Lee E, Dalgarno L, Strauss EG et al (1987) Conserved elements in the 3′ untranslated region of flavivirus RNAs and potential cyclization sequences. J Mol Biol 198(1):33–41
Halwani R, Cen S, Javanbakht H, Saadatmand J, Kim S, Shiba K et al (2004) Cellular distribution of Lysyl-tRNA synthetase and its interaction with Gag during human immunodeficiency virus type 1 assembly. J Virol 78(14):7553–7564
Hargittai MR, Mangla AT, Gorelick RJ, Musier-Forsyth K (2001) HIV-1 nucleocapsid protein zinc finger structures induce tRNA(Lys,3) structural changes but are not critical for primer/template annealing. J Mol Biol 312(5):985–997
Hargittai MR, Gorelick RJ, Rouzina I, Musier-Forsyth K (2004) Mechanistic insights into the kinetics of HIV-1 nucleocapsid protein-facilitated tRNA annealing to the primer binding site. J Mol Biol 337(4):951–968
Harris JD, Scott JV, Traynor B, Brahic M, Stowring L, Ventura P et al (1981) Visna virus DNA: discovery of a novel gapped structure. Virology 113(2):573–583
Hauber J, Cullen BR (1988) Mutational analysis of the trans-activation-responsive region of the human immunodeficiency virus type I long terminal repeat. J Virol 62(3):673–679
Heinzinger NK, Bukinsky MI, Haggerty SA, Ragland AM, Kewalramani V, Lee MA et al (1994) The Vpr protein of human immunodeficiency virus type 1 influences nuclear localization of viral nucleic acids in nondividing host cells. Proc Natl Acad Sci USA 91(15):7311–7315
Henriet S, Sinck L, Bec G, Gorelick RJ, Marquet R, Paillart JC (2007) Vif is a RNA chaperone that could temporally regulate RNA dimerization and the early steps of HIV-1 reverse transcription. Nucleic Acids Res 35(15):5141–5153
Heyman T, Agoutin B, Friant S, Wilhelm FX, Wilhelm ML (1995) 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 253(2):291–303
Hostomsky Z, Hostomska Z, Fu TB, Taylor J (1992) Reverse transcriptase of human immunodeficiency virus type 1: functionality of subunits of the heterodimer in DNA synthesis. J Virol 66(5):3179–3182
Huang Y, Mak J, Cao Q, Li Z, Wainberg MA, Kleiman L (1994) Incorporation of excess wild-type and mutant tRNA(3Lys) into human immunodeficiency virus type 1. J Virol 68(12): 7676–7683
Huang Y, Wang J, Shalom A, Li Z, Khorchid A, Wainberg MA et al (1997) Primer tRNA3Lys on the viral genome exists in unextended and two-base extended forms within mature human immunodeficiency virus type 1. J Virol 71(1):726–728
Huber HE, Richardson CC (1990) Processing of the primer for plus strand DNA synthesis by human immunodeficiency virus 1 reverse transcriptase. J Biol Chem 265(18):10565–10573
Hungnes O, Tjotta E, Grinde B (1992) Mutations in the central polypurine tract of HIV-1 result in delayed replication. Virology 190(1):440–442
Isel C, Marquet R, Keith G, Ehresmann C, Ehresmann B (1993) Modified nucleotides of tRNA(3Lys) modulate primer/template loop-loop interaction in the initiation complex of HIV-1 reverse transcription. J Biol Chem 268(34):25269–25272
Isel C, Ehresmann C, Keith G, Ehresmann B, Marquet R (1995) Initiation of reverse transcription of HIV-1: secondary structure of the HIV-1 RNA/tRNA(3Lys) (template/primer). J Mol Biol 247(2):236–250
Isel C, Lanchy JM, Le Grice SF, Ehresmann C, Ehresmann B, Marquet R (1996) Specific initiation and switch to elongation of human immunodeficiency virus type 1 reverse transcription require the post-transcriptional modifications of primer tRNA3Lys. EMBO J 15(4):917–924
Isel C, Keith G, Ehresmann B, Ehresmann C, Marquet R (1998) Mutational analysis of the tRNA3Lys/HIV-1 RNA (primer/template) complex. Nucleic Acids Res 26(5):1198–1204
Isel C, Ehresmann C, Marquet R (2010) Initiation of HIV reverse transcription. Viruses 2:213–243
Jacobo-Molina A, Clark AD Jr, Williams RL, Nanni RG, Clark P, Ferris AL et al (1991) Crystals of a ternary complex of human immunodeficiency virus type 1 reverse transcriptase with a monoclonal antibody Fab fragment and double-stranded DNA diffract x-rays to 3.5-A resolution. Proc Natl Acad Sci USA 88(23):10895–10899
Jacobo-Molina A, Ding J, Nanni RG, Clark AD Jr, Lu X, Tantillo C et al (1993) Crystal structure of human immunodeficiency virus type 1 reverse transcriptase complexed with double-stranded DNA at 3.0 A resolution shows bent DNA. Proc Natl Acad Sci USA 90(13):6320–6324
Javanbakht H, Cen S, Musier-Forsyth K, Kleiman L (2002) Correlation between tRNALys3 aminoacylation and its incorporation into HIV-1. J Biol Chem 277(20):17389–17396
Jetzt AE, Yu H, Klarmann GJ, Ron Y, Preston BD, Dougherty JP (2000) High rate of recombination throughout the human immunodeficiency virus type 1 genome. J Virol 74(3):1234–1240
Jiang M, Mak J, Ladha A, Cohen E, Klein M, Rovinski B et al (1993) Identification of tRNAs incorporated into wild-type and mutant human immunodeficiency virus type 1. J Virol 67(6):3246–3253
Johnson PE, Turner RB, Wu ZR, Hairston L, Guo J, Levin JG et al (2000) A mechanism for plus-strand transfer enhancement by the HIV-1 nucleocapsid protein during reverse transcription. Biochemistry 39(31):9084–9091
Jones FD, Hughes SH (2007) In vitro analysis of the effects of mutations in the G-tract of the human immunodeficiency virus type 1 polypurine tract on RNase H cleavage specificity. Virology 360(2):341–349
Julias JG, Ferris AL, Boyer PL, Hughes SH (2001) Replication of phenotypically mixed human immunodeficiency virus type 1 virions containing catalytically active and catalytically inactive reverse transcriptase. J Virol 75(14):6537–6546
Julias JG, McWilliams MJ, Sarafianos SG, Arnold E, Hughes SH (2002) Mutations in the RNase H domain of HIV-1 reverse transcriptase affect the initiation of DNA synthesis and the specificity of RNase H cleavage in vivo. Proc Natl Acad Sci USA 99(14):9515–9520
Junghans RP, Boone LR, Skalka AM (1982) Products of reverse transcription in avian retrovirus analyzed by electron microscopy. J Virol 43(2):544–554
Kaminska M, Shalak V, Francin M, Mirande M (2007) Viral hijacking of mitochondrial lysyl-tRNA synthetase. J Virol 81(1):68–73
Kang SM, Zhang Z, Morrow CD (1997) Identification of a sequence within U5 required for human immunodeficiency virus type 1 to stably maintain a primer binding site complementary to tRNA(Met). J Virol 71(1):207–217
Khorchid A, Javanbakht H, Wise S, Halwani R, Parniak MA, Wainberg MA et al (2000) Sequences within Pr160gag-pol affecting the selective packaging of primer tRNA(Lys3) into HIV-1. J Mol Biol 299(1):17–26
Kim JK, Palaniappan C, Wu W, Fay PJ, Bambara RA (1997) Evidence for a unique mechanism of strand transfer from the transactivation response region of HIV-1. J Biol Chem 272(27): 16769–16777
Klasens BI, Huthoff HT, Das AT, Jeeninga RE, Berkhout B (1999) The effect of template RNA structure on elongation by HIV-1 reverse transcriptase. Biochim Biophys Acta 1444(3):355–370
Kleiman L, Jones CP, Musier-Forsyth K (2010) Formation of the tRNALys packaging complex in HIV-1. FEBS Lett 584(2):359–365
Kohlstaedt LA, Wang J, Friedman JM, Rice PA, Steitz TA (1992) Crystal structure at 3.5 A resolution of HIV-1 reverse transcriptase complexed with an inhibitor. Science 256(5065): 1783–1790
Lanchy JM, Ehresmann C, Le Grice SF, Ehresmann B, Marquet R (1996) Binding and kinetic properties of HIV-1 reverse transcriptase markedly differ during initiation and elongation of reverse transcription. EMBO J 15(24):7178–7187
Lanchy JM, Keith G, Le Grice SF, Ehresmann B, Ehresmann C, Marquet R (1998) Contacts between reverse transcriptase and the primer strand govern the transition from initiation to elongation of HIV-1 reverse transcription. J Biol Chem 273(38):24425–24432
Lapadat-Tapolsky M, Gabus C, Rau M, Darlix JL (1997) Possible roles of HIV-1 nucleocapsid protein in the specificity of proviral DNA synthesis and in its variability. J Mol Biol 268(2):250–260
Lavigne M, Buc H (1999) Compression of the DNA minor groove is responsible for termination of DNA synthesis by HIV-1 reverse transcriptase. J Mol Biol 285(3):977–995
Lavigne M, Roux P, Buc H, Schaeffer F (1997) DNA curvature controls termination of plus strand DNA synthesis at the centre of HIV-1 genome. J Mol Biol 266(3):507–524
Le Grice SF, Gruninger-Leitch F (1990) Rapid purification of homodimer and heterodimer HIV-1 reverse transcriptase by metal chelate affinity chromatography. Eur J Biochem 187(2):307–314
Le Grice SF, Naas T, Wohlgensinger B, Schatz O (1991) Subunit-selective mutagenesis indicates minimal polymerase activity in heterodimer-associated p51 HIV-1 reverse transcriptase. EMBO J 10(12):3905–3911
Leavitt AD, Rose RB, Varmus HE (1992) Both substrate and target oligonucleotide sequences affect in vitro integration mediated by human immunodeficiency virus type 1 integrase protein produced in Saccharomyces cerevisiae. J Virol 66(4):2359–2368
Levin JG, Mitra M, Mascarenhas A, Musier-Forsyth K (2010) Role of HIV-1 nucleocapsid protein in HIV-1 reverse transcription. RNA Biol 7(6):754–774
Levy DN, Aldrovandi GM, Kutsch O, Shaw GM (2004) Dynamics of HIV-1 recombination in its natural target cells. Proc Natl Acad Sci USA 101(12):4204–4209
Li X, Mak J, Arts EJ, Gu Z, Kleiman L, Wainberg MA et al (1994) Effects of alterations of primer-binding site sequences on human immunodeficiency virus type 1 replication. J Virol 68(10): 6198–6206
Li Y, Zhang Z, Wakefield JK, Kang SM, Morrow CD (1997) Nucleotide substitutions within U5 are critical for efficient reverse transcription of human immunodeficiency virus type 1 with a primer binding site complementary to tRNA(His). J Virol 71(9):6315–6322
Li L, Olvera JM, Yoder KE, Mitchell RS, Butler SL, Lieber M et al (2001) Role of the non-homologous DNA end joining pathway in the early steps of retroviral infection. EMBO J 20(12):3272–3281
Liu S, Harada BT, Miller JT, Le Grice SF, Zhuang X (2010) Initiation complex dynamics direct the transitions between distinct phases of early HIV reverse transcription. Nat Struct Mol Biol 17(12):1453–1460
Mak J, Jiang M, Wainberg MA, Hammarskjold ML, Rekosh D, Kleiman L (1994) Role of Pr160gag-pol in mediating the selective incorporation of tRNA(Lys) into human immunodeficiency virus type 1 particles. J Virol 68(4):2065–2072
Masuda T, Kuroda MJ, Harada S (1998) Specific and independent recognition of U3 and U5 att sites by human immunodeficiency virus type 1 integrase in vivo. J Virol 72(10):8396–8402
McDonald D, Vodicka MA, Lucero G, Svitkina TM, Borisy GG, Emerman M et al (2002) Visualization of the intracellular behavior of HIV in living cells. J Cell Biol 159(3):441–452
Miles LR, Agresta BE, Khan MB, Tang S, Levin JG, Powell MD (2005) Effect of polypurine tract (PPT) mutations on human immunodeficiency virus type 1 replication: a virus with a completely randomized PPT retains low infectivity. J Virol 79(11):6859–6867
Miller WA, White KA (2006) Long-distance RNA-RNA interactions in plant virus gene expression and replication. Annu Rev Phytopathol 44:447–467
Miller MD, Farnet CM, Bushman FD (1997) Human immunodeficiency virus type 1 preintegration complexes: studies of organization and composition. J Virol 71(7):5382–5390
Moore-Rigdon KL, Kosloff BR, Kirkman RL, Morrow CD (2005) Preferences for the selection of unique tRNA primers revealed from analysis of HIV-1 replication in peripheral blood mononuclear cells. Retrovirology 2:21
Muesing MA, Smith DH, Cabradilla CD, Benton CV, Lasky LA, Capon DJ (1985) Nucleic acid structure and expression of the human AIDS/lymphadenopathy retrovirus. Nature 313(6002):450–458
Muesing MA, Smith DH, Capon DJ (1987) Regulation of mRNA accumulation by a human immunodeficiency virus trans-activator protein. Cell 48(4):691–701
Muthuswami R, Chen J, Burnett BP, Thimmig RL, Janjic N, McHenry CS (2002) The HIV plus-strand transfer reaction: determination of replication-competent intermediates and identification of a novel lentiviral element, the primer over-extension sequence. J Mol Biol 315(3):311–323
Negroni M, Buc H (2000) Copy-choice recombination by reverse transcriptases: reshuffling of genetic markers mediated by RNA chaperones. Proc Natl Acad Sci USA 97(12):6385–6390
Nermut MV, Fassati A (2003) Structural analyses of purified human immunodeficiency virus type 1 intracellular reverse transcription complexes. J Virol 77(15):8196–8206
Ooms M, Abbink TE, Pham C, Berkhout B (2007) Circularization of the HIV-1 RNA genome. Nucleic Acids Res 35(15):5253–5261
Palaniappan C, Fuentes GM, Rodriguez-Rodriguez L, Fay PJ, Bambara RA (1996) Helix structure and ends of RNA/DNA hybrids direct the cleavage specificity of HIV-1 reverse transcriptase RNase H. J Biol Chem 271(4):2063–2070
Pereira LA, Bentley K, Peeters A, Churchill MJ, Deacon NJ (2000) A compilation of cellular transcription factor interactions with the HIV-1 LTR promoter. Nucleic Acids Res 28(3): 663–668
Piekna-Przybylska D, Bambara RA (2011) Requirements for efficient minus strand strong-stop DNA transfer in human immunodeficiency virus 1. RNA Biol 8(2):230–236
Piekna-Przybylska D, DiChiacchio L, Mathews DH, Bambara RA (2010) A sequence similar to tRNA 3 Lys gene is embedded in HIV-1 U3-R and promotes minus-strand transfer. Nat Struct Mol Biol 17(1):83–89
Piekna-Przybylska D, Dykes C, Demeter LM, Bambara RA (2011) Sequences in the U3 region of human immunodeficiency virus 1 improve efficiency of minus strand transfer in infected cells. Virology 410(2):368–374
Powell MD, Levin JG (1996) Sequence and structural determinants required for priming of plus-strand DNA synthesis by the human immunodeficiency virus type 1 polypurine tract. J Virol 70(8):5288–5296
Pullen KA, Rattray AJ, Champoux JJ (1993) The sequence features important for plus strand priming by human immunodeficiency virus type 1 reverse transcriptase. J Biol Chem 268(9): 6221–6227
Ramalanjaona N, de Rocquigny H, Millet A, Ficheux D, Darlix JL, Mely Y (2007) Investigating the mechanism of the nucleocapsid protein chaperoning of the second strand transfer during HIV-1 DNA synthesis. J Mol Biol 374(4):1041–1053
Ramirez de Arellano E, Soriano V, Alcamil J, Holguin A (2006) New findings on transcription regulation across different HIV-1 subtypes. AIDS Rev 8(1):9–16
Rausch JW, Le Grice SF (2004) ‘Binding, bending and bonding’: polypurine tract-primed initiation of plus-strand DNA synthesis in human immunodeficiency virus. Int J Biochem Cell Biol 36(9):1752–1766
Renda MJ, Rosenblatt JD, Klimatcheva E, Demeter LM, Bambara RA, Planelles V (2001) Mutation of the methylated tRNA(Lys)(3) residue A58 disrupts reverse transcription and inhibits replication of human immunodeficiency virus type 1. J Virol 75(20):9671–9678
Renda MJ, Bradel-Tretheway B, Planelles V, Bambara RA, Dewhurst S (2004) Inhibition of HIV type 1 replication using lentiviral-mediated delivery of mutant tRNA(Lys3)A58U. AIDS Res Hum Retroviruses 20(12):1324–1334
Rhim H, Park J, Morrow CD (1991) Deletions in the tRNA(Lys) primer-binding site of human immunodeficiency virus type 1 identify essential regions for reverse transcription. J Virol 65(9):4555–4564
Romero-Lopez C, Berzal-Herranz A (2009) A long-range RNA-RNA interaction between the 5′ and 3′ ends of the HCV genome. RNA 15(9):1740–1752
Rumbaugh JA, Fuentes GM, Bambara RA (1998) Processing of an HIV replication intermediate by the human DNA replication enzyme FEN1. J Biol Chem 273(44):28740–28745
Saadatmand J, Niu M, Kleiman L, Guo F (2009) The contribution of the primer activation signal to differences between Gag- and NCp7-facilitated tRNA(Lys3) annealing in HIV-1. Virology 391(2):334–341
Sarafianos SG, Das K, Tantillo C, Clark AD Jr, Ding J, Whitcomb JM et al (2001) Crystal structure of HIV-1 reverse transcriptase in complex with a polypurine tract RNA:DNA. EMBO J 20(6):1449–1461
Schultz SJ, Champoux JJ (2008) RNase H activity: structure, specificity, and function in reverse transcription. Virus Res 134(1–2):86–103
Schultz SJ, Zhang M, Champoux JJ (2004) Recognition of internal cleavage sites by retroviral RNases H. J Mol Biol 344(3):635–652
Selby MJ, Bain ES, Luciw PA, Peterlin BM (1989) Structure, sequence, and position of the stem-loop in tar determine transcriptional elongation by tat through the HIV-1 long terminal repeat. Genes Dev 3(4):547–558
Serrano P, Pulido MR, Saiz M, Martinez-Salas E (2006) The 3′ end of the foot-and-mouth disease virus genome establishes two distinct long-range RNA-RNA interactions with the 5′ end region. J Gen Virol 87(Pt 10):3013–3022
Shank PR, Hughes SH, Kung HJ, Majors JE, Quintrell N, Guntaka RV et al (1978) Mapping unintegrated avian sarcoma virus DNA: termini of linear DNA bear 300 nucleotides present once or twice in two species of circular DNA. Cell 15(4):1383–1395
Shen W, Gao L, Balakrishnan M, Bambara RA (2009) A recombination hot spot in HIV-1 contains guanosine runs that can form a G-quartet structure and promote strand transfer in vitro. J Biol Chem 284(49):33883–33893
Sherman PA, Fyfe JA (1990) Human immunodeficiency virus integration protein expressed in Escherichia coli possesses selective DNA cleaving activity. Proc Natl Acad Sci USA 87(13):5119–5123
Shurtleff AC, Beasley DW, Chen JJ, Ni H, Suderman MT, Wang H et al (2001) Genetic variation in the 3′ non-coding region of dengue viruses. Virology 281(1):75–87
Skripkin E, Isel C, Marquet R, Ehresmann B, Ehresmann C (1996) Psoralen crosslinking between human immunodeficiency virus type 1 RNA and primer tRNA3(Lys). Nucleic Acids Res 24(3): 509–514
Smith CM, Smith JS, Roth MJ (1999) RNase H requirements for the second strand transfer reaction of human immunodeficiency virus type 1 reverse transcription. J Virol 73(8):6573–6581
Song M, Basu VP, Hanson MN, Roques BP, Bambara RA (2008) Proximity and branch migration mechanisms in HIV-1 minus strand strong stop DNA transfer. J Biol Chem 283(6): 3141–3150
Stetor SR, Rausch JW, Guo MJ, Burnham JP, Boone LR, Waring MJ et al (1999) Characterization of (+) strand initiation and termination sequences located at the center of the equine infectious anemia virus genome. Biochemistry 38(12):3656–3667
Suzuki Y, Craigie R (2007) The road to chromatin – nuclear entry of retroviruses. Nat Rev Microbiol 5(3):187–196
Svarovskaia ES, Delviks KA, Hwang CK, Pathak VK (2000) Structural determinants of murine leukemia virus reverse transcriptase that affect the frequency of template switching. J Virol 74(15):7171–7178
Svarovskaia ES, Barr R, Zhang X, Pais GC, Marchand C, Pommier Y et al (2004) Azido-containing diketo acid derivatives inhibit human immunodeficiency virus type 1 integrase in vivo and influence the frequency of deletions at two-long-terminal-repeat-circle junctions. J Virol 78(7): 3210–3222
Thrall SH, Reinstein J, Wohrl BM, Goody RS (1996) Evaluation of human immunodeficiency virus type 1 reverse transcriptase primer tRNA binding by fluorescence spectroscopy: specificity and comparison to primer/template binding. Biochemistry 35(14):4609–4618
Tisne C, Roques BP, Dardel F (2004) The annealing mechanism of HIV-1 reverse transcription primer onto the viral genome. J Biol Chem 279(5):3588–3595
Tobaly-Tapiero J, Kupiec JJ, Santillana-Hayat M, Canivet M, Peries J, Emanoil-Ravier R (1991) Further characterization of the gapped DNA intermediates of human spumavirus: evidence for a dual initiation of plus-strand DNA synthesis. J Gen Virol 72(Pt 3):605–608
Vink C, van Gent DC, Elgersma Y, Plasterk RH (1991) Human immunodeficiency virus integrase protein requires a subterminal position of its viral DNA recognition sequence for efficient cleavage. J Virol 65(9):4636–4644
Vogt VM (1997) Retroviral virions and genomes. In: Coffin JM, Hughes SM, Varmus HE (eds) Retroviruses (25 March 2011 ed.). Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, pp. 27–69
Wakefield JK, Wolf AG, Morrow CD (1995) Human immunodeficiency virus type 1 can use different tRNAs as primers for reverse transcription but selectively maintains a primer binding site complementary to tRNA(3Lys). J Virol 69(10):6021–6029
Wakefield JK, Kang SM, Morrow CD (1996) Construction of a type 1 human immunodeficiency virus that maintains a primer binding site complementary to tRNA(His). J Virol 70(2): 966–975
Wei SQ, Mizuuchi K, Craigie R (1998) Footprints on the viral DNA ends in Moloney murine leukemia virus preintegration complexes reflect a specific association with integrase. Proc Natl Acad Sci USA 95(18):10535–10540
Wei M, Cen S, Niu M, Guo F, Kleiman L (2005) Defective replication in human immunodeficiency virus type 1 when non-primers are used for reverse transcription. J Virol 79(14):9081–9087
Wills NM, Gesteland RF, Atkins JF (1994) Pseudoknot-dependent read-through of retroviral gag termination codons: importance of sequences in the spacer and loop 2. EMBO J 13(17): 4137–4144
Wisniewski M, Balakrishnan M, Palaniappan C, Fay PJ, Bambara RA (2000a) The sequential mechanism of HIV reverse transcriptase RNase H. J Biol Chem 275(48):37664–37671
Wisniewski M, Balakrishnan M, Palaniappan C, Fay PJ, Bambara RA (2000b) Unique progressive cleavage mechanism of HIV reverse transcriptase RNase H. Proc Natl Acad Sci USA 97(22):11978–11983
Wohrl BM, Moelling K (1990) Interaction of HIV-1 ribonuclease H with polypurine tract containing RNA-DNA hybrids. Biochemistry 29(44):10141–10147
Wu T, Guo J, Bess J, Henderson LE, Levin JG (1999) Molecular requirements for human immunodeficiency virus type 1 plus-strand transfer: analysis in reconstituted and endogenous reverse transcription systems. J Virol 73(6):4794–4805
Yusupova G, Lanchy JM, Yusupov M, Keith G, Le Grice SF, Ehresmann C et al (1996) Primer selection by HIV-1 reverse transcriptase on RNA-tRNA(3Lys) and DNA-tRNA(3Lys) hybrids. J Mol Biol 261(3):315–321
Zaitseva L, Myers R, Fassati A (2006) tRNAs promote nuclear import of HIV-1 intracellular reverse transcription complexes. PLoS Biol 4(10):e332
Zhang Z, Kang SM, LeBlanc A, Hajduk SL, Morrow CD (1996) Nucleotide sequences within the U5 region of the viral RNA genome are the major determinants for an human immunodeficiency virus type 1 to maintain a primer binding site complementary to tRNA(His). Virology 226(2):306–317
Zhang J, Tang LY, Li T, Ma Y, Sapp CM (2000) Most retroviral recombinations occur during minus-strand DNA synthesis. J Virol 74(5):2313–2322
Zhuang J, Jetzt AE, Sun G, Yu H, Klarmann G, Ron Y et al (2002) Human immunodeficiency virus type 1 recombination: rate, fidelity, and putative hot spots. J Virol 76(22):11273–11282
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Piekna-Przybylska, D., Bambara, R.A. (2013). Proviral DNA Synthesis in HIV: Background. In: LeGrice, S., Gotte, M. (eds) Human Immunodeficiency Virus Reverse Transcriptase. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-7291-9_2
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