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Packaging of the HIV-1 RNA Genome

  • Jianbo Chen
  • Olga A. Nikolaitchik
  • Kari A. Dilley
  • Wei-Shau Hu
Chapter

Abstract

Encapsidating the viral genome into virions is an essential step in generating infectious viral particles. Most HIV-1 particles contain two copies of full-length viral RNA indicating genome encapsidation is an efficient and regulated process. Interactions between the HIV-1 structural protein Gag and cis-acting elements in the viral RNA mediate the packaging of viral RNA. The HIV-1 genome selects its copackaged RNA partner, or dimerizes, prior to encapsidation. Several aspects of virus biology and host–virus interactions important for the packaging of HIV-1 viral genomes are discussed in this review.

Keywords

Murine Leukemia Virus Mouse Mammary Tumor Virus Total Internal Reflection Fluorescence Microscopy Constitutive Transport Element Dimerization Initiation Signal 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Chen J, Nikolaitchik O, Singh J, Wright A, Bencsics CE, Coffin JM et al (2009) High efficiency of HIV-1 genomic RNA packaging and heterozygote formation revealed by single virion analysis. Proc Natl Acad Sci U S A 106(32):13535–13540PubMedGoogle Scholar
  2. 2.
    Freed EO, Martin MA (2007) HIVs and their replication. In: Knipe DM, Howley PM (eds) Fields virology, 5th edn. Lippincott, Williams, & Wilkins, Philadelphia, PA, pp 2107–2185Google Scholar
  3. 3.
    Lever A, Gottlinger H, Haseltine W, Sodroski J (1989) Identification of a sequence required for efficient packaging of human immunodeficiency virus type 1 RNA into virions. J Virol 63(9):4085–4087PubMedGoogle Scholar
  4. 4.
    Olsen HS, Nelbock P, Cochrane AW, Rosen CA (1990) Secondary structure is the major determinant for interaction of HIV rev protein with RNA. Science 247(4944):845–848PubMedGoogle Scholar
  5. 5.
    Abbink TE, Berkhout B (2003) A novel long distance base-pairing interaction in human immunodeficiency virus type 1 RNA occludes the Gag start codon. J Biol Chem 278(13):11601–11611PubMedGoogle Scholar
  6. 6.
    Berkhout B (1996) Structure and function of the human immunodeficiency virus leader RNA. Prog Nucleic Acid Res Mol Biol 54:1–34PubMedGoogle Scholar
  7. 7.
    Berkhout B, van Wamel JL (2000) The leader of the HIV-1 RNA genome forms a compactly folded tertiary structure. RNA 6(2):282–295PubMedGoogle Scholar
  8. 8.
    Paillart JC, Dettenhofer M, Yu XF, Ehresmann C, Ehresmann B, Marquet R (2004) First snapshots of the HIV-1 RNA structure in infected cells and in virions. J Biol Chem 279(46):48397–48403PubMedGoogle Scholar
  9. 9.
    Lu K, Heng X, Garyu L, Monti S, Garcia EL, Kharytonchyk S et al (2011) NMR detection of structures in the HIV-1 5′-leader RNA that regulate genome packaging. Science 334(6053):242–245PubMedGoogle Scholar
  10. 10.
    Watts JM, Dang KK, Gorelick RJ, Leonard CW, Bess JW Jr, Swanstrom R et al (2009) Architecture and secondary structure of an entire HIV-1 RNA genome. Nature 460(7256):711–716PubMedGoogle Scholar
  11. 11.
    Wilkinson KA, Gorelick RJ, Vasa SM, Guex N, Rein A, Mathews DH et al (2008) High-throughput SHAPE analysis reveals structures in HIV-1 genomic RNA strongly conserved across distinct biological states. PLoS Biol 6(4):e96PubMedGoogle Scholar
  12. 12.
    Clever J, Sassetti C, Parslow TG (1995) RNA secondary structure and binding sites for gag gene products in the 5′ packaging signal of human immunodeficiency virus type 1. J Virol 69(4):2101–2109PubMedGoogle Scholar
  13. 13.
    Clever JL, Miranda D Jr, Parslow TG (2002) RNA structure and packaging signals in the 5′ leader region of the human immunodeficiency virus type 1 genome. J Virol 76(23):12381–12387PubMedGoogle Scholar
  14. 14.
    McBride MS, Panganiban AT (1996) The human immunodeficiency virus type 1 encapsidation site is a multipartite RNA element composed of functional hairpin structures. J Virol 70(5):2963–2973PubMedGoogle Scholar
  15. 15.
    Sakuragi J, Iwamoto A, Shioda T (2002) Dissociation of genome dimerization from packaging functions and virion maturation of human immunodeficiency virus type 1. J Virol 76(3):959–967PubMedGoogle Scholar
  16. 16.
    Clavel F, Orenstein JM (1990) A mutant of human immunodeficiency virus with reduced RNA packaging and abnormal particle morphology. J Virol 64(10):5230–5234PubMedGoogle Scholar
  17. 17.
    Hayashi T, Shioda T, Iwakura Y, Shibuta H (1992) RNA packaging signal of human immunodeficiency virus type 1. Virology 188(2):590–599PubMedGoogle Scholar
  18. 18.
    Baudin F, Marquet R, Isel C, Darlix JL, Ehresmann B, Ehresmann C (1993) Functional sites in the 5′ region of human immunodeficiency virus type 1 RNA form defined structural domains. J Mol Biol 229(2):382–397PubMedGoogle Scholar
  19. 19.
    Clever JL, Parslow TG (1997) Mutant human immunodeficiency virus type 1 genomes with defects in RNA dimerization or encapsidation. J Virol 71(5):3407–3414PubMedGoogle Scholar
  20. 20.
    Parolin C, Dorfman T, Palu G, Gottlinger H, Sodroski J (1994) Analysis in human immunodeficiency virus type 1 vectors of cis-acting sequences that affect gene transfer into human lymphocytes. J Virol 68(6):3888–3895PubMedGoogle Scholar
  21. 21.
    Luban J, Goff SP (1994) Mutational analysis of cis-acting packaging signals in human immunodeficiency virus type 1 RNA. J Virol 68(6):3784–3793PubMedGoogle Scholar
  22. 22.
    Laham-Karam N, Bacharach E (2007) Transduction of human immunodeficiency virus type 1 vectors lacking encapsidation and dimerization signals. J Virol 81(19):10687–10698PubMedGoogle Scholar
  23. 23.
    Duesberg PH (1968) Physical properties of Rous Sarcoma Virus RNA. Proc Natl Acad Sci U S A 60(4):1511–1518PubMedGoogle Scholar
  24. 24.
    Kung HJ, Hu S, Bender W, Bailey JM, Davidson N, Nicolson MO et al (1976) RD-114, baboon, and woolly monkey viral RNA’s compared in size and structure. Cell 7(4):609–620PubMedGoogle Scholar
  25. 25.
    Hu WS, Temin HM (1990) Genetic consequences of packaging two RNA genomes in one retroviral particle: pseudodiploidy and high rate of genetic recombination. Proc Natl Acad Sci U S A 87(4):1556–1560PubMedGoogle Scholar
  26. 26.
    Temin HM (1991) Sex and recombination in retroviruses. Trends Genet 7(3):71–74PubMedGoogle Scholar
  27. 27.
    Hwang CK, Svarovskaia ES, Pathak VK (2001) Dynamic copy choice: steady state between murine leukemia virus polymerase and polymerase-dependent RNase H activity determines frequency of in vivo template switching. Proc Natl Acad Sci U S A 98(21):12209–12214PubMedGoogle Scholar
  28. 28.
    Coffin JM (1979) Structure, replication, and recombination of retrovirus genomes: some unifying hypotheses. J Gen Virol 42(1):1–26PubMedGoogle Scholar
  29. 29.
    Ikawa Y, Ross J, Leder P (1974) An association between globin messenger RNA and 60S RNA derived from Friend leukemia virus. Proc Natl Acad Sci U S A 71(4):1154–1158PubMedGoogle Scholar
  30. 30.
    Gallis B, Linial M, Eisenman R (1979) An avian oncovirus mutant deficient in genomic RNA: characterization of the packaged RNA as cellular messenger RNA. Virology 94(1):146–161PubMedGoogle Scholar
  31. 31.
    Aronoff R, Linial M (1991) Specificity of retroviral RNA packaging. J Virol 65(1):71–80PubMedGoogle Scholar
  32. 32.
    Adkins B, Hunter T (1981) Identification of a packaged cellular mRNA in virions of rous sarcoma virus. J Virol 39(2):471–480PubMedGoogle Scholar
  33. 33.
    Muriaux D, Mirro J, Harvin D, Rein A (2001) RNA is a structural element in retrovirus particles. Proc Natl Acad Sci U S A 98(9):5246–5251PubMedGoogle Scholar
  34. 34.
    Rulli SJ Jr, Hibbert CS, Mirro J, Pederson T, Biswal S, Rein A (2007) Selective and nonselective packaging of cellular RNAs in retrovirus particles. J Virol 81(12):6623–6631PubMedGoogle Scholar
  35. 35.
    Barat C, Lullien V, Schatz O, Keith G, Nugeyre MT, Gruninger-Leitch F et al (1989) HIV-1 reverse transcriptase specifically interacts with the anticodon domain of its cognate primer tRNA. EMBO J 8(11):3279–3285PubMedGoogle Scholar
  36. 36.
    Sallafranque-Andreola ML, Robert D, Barr PJ, Fournier M, Litvak S, Sarih-Cottin L et al (1989) Human immunodeficiency virus reverse transcriptase expressed in transformed yeast cells. Biochemical properties and interactions with bovine tRNALys. Eur J Biochem 184(2):367–374PubMedGoogle Scholar
  37. 37.
    Onafuwa-Nuga AA, Telesnitsky A, King SR (2006) 7SL RNA, but not the 54-kd signal recognition particle protein, is an abundant component of both infectious HIV-1 and minimal virus-like particles. RNA 12(4):542–546PubMedGoogle Scholar
  38. 38.
    Didierlaurent L, Racine PJ, Houzet L, Chamontin C, Berkhout B, Mougel M (2011) Role of HIV-1 RNA and protein determinants for the selective packaging of spliced and unspliced viral RNA and host U6 and 7SL RNA in virus particles. Nucleic Acids Res 39(20):8915–8927PubMedGoogle Scholar
  39. 39.
    Keene SE, King SR, Telesnitsky A (2010) 7SL RNA is retained in HIV-1 minimal virus-like particles as an S-domain fragment. J Virol 84(18):9070–9077PubMedGoogle Scholar
  40. 40.
    Kaplan AH, Manchester M, Swanstrom R (1994) The activity of the protease of human immunodeficiency virus type 1 is initiated at the membrane of infected cells before the release of viral proteins and is required for release to occur with maximum efficiency. J Virol 68(10):6782–6786PubMedGoogle Scholar
  41. 41.
    Alfadhli A, McNett H, Tsagli S, Bachinger HP, Peyton DH, Barklis E (2011) HIV-1 matrix protein binding to RNA. J Mol Biol 410(4):653–666PubMedGoogle Scholar
  42. 42.
    Chukkapalli V, Oh SJ, Ono A (2010) Opposing mechanisms involving RNA and lipids regulate HIV-1 Gag membrane binding through the highly basic region of the matrix domain. Proc Natl Acad Sci U S A 107(4):1600–1605PubMedGoogle Scholar
  43. 43.
    Jones CP, Datta SA, Rein A, Rouzina I, Musier-Forsyth K (2011) Matrix domain modulates HIV-1 Gag’s nucleic acid chaperone activity via inositol phosphate binding. J Virol 85(4):1594–1603PubMedGoogle Scholar
  44. 44.
    Rein A (2010) Nucleic acid chaperone activity of retroviral Gag proteins. RNA Biol 7(6):700–705PubMedGoogle Scholar
  45. 45.
    Purohit P, Dupont S, Stevenson M, Green MR (2001) Sequence-specific interaction between HIV-1 matrix protein and viral genomic RNA revealed by in vitro genetic selection. RNA 7(4):576–584PubMedGoogle Scholar
  46. 46.
    Fauquet CM, Mayo MA, Maniloff J, Desselberger U, Ball LA (2005) Virus Taxonomy, Eighth Report of the International Committee on Taxonomy of Viruses. Elsevier Academic Press.Google Scholar
  47. 47.
    Aldovini A, Young RA (1990) Mutations of RNA and protein sequences involved in human immunodeficiency virus type 1 packaging result in production of noninfectious virus. J Virol 64(5):1920–1926PubMedGoogle Scholar
  48. 48.
    Gorelick RJ, Chabot DJ, Rein A, Henderson LE, Arthur LO (1993) The two zinc fingers in the human immunodeficiency virus type 1 nucleocapsid protein are not functionally equivalent. J Virol 67(7):4027–4036PubMedGoogle Scholar
  49. 49.
    Gorelick RJ, Nigida SM Jr, Bess JW Jr, Arthur LO, Henderson LE, Rein A (1990) Noninfectious human immunodeficiency virus type 1 mutants deficient in genomic RNA. J Virol 64(7):3207–3211PubMedGoogle Scholar
  50. 50.
    Meric C, Gouilloud E, Spahr PF (1988) Mutations in Rous sarcoma virus nucleocapsid protein p12 (NC): deletions of Cys-His boxes. J Virol 62(9):3328–3333PubMedGoogle Scholar
  51. 51.
    Meric C, Goff SP (1989) Characterization of Moloney murine leukemia virus mutants with single-amino-acid substitutions in the Cys-His box of the nucleocapsid protein. J Virol 63(4):1558–1568PubMedGoogle Scholar
  52. 52.
    Poon DT, Wu J, Aldovini A (1996) Charged amino acid residues of human immunodeficiency virus type 1 nucleocapsid p7 protein involved in RNA packaging and infectivity. J Virol 70(10):6607–6616PubMedGoogle Scholar
  53. 53.
    Kafaie J, Song R, Abrahamyan L, Mouland AJ, Laughrea M (2008) Mapping of nucleocapsid residues important for HIV-1 genomic RNA dimerization and packaging. Virology 375(2):592–610PubMedGoogle Scholar
  54. 54.
    Mark-Danieli M, Laham N, Kenan-Eichler M, Castiel A, Melamed D, Landau M et al (2005) Single point mutations in the zinc finger motifs of the human immunodeficiency virus type 1 nucleocapsid alter RNA binding specificities of the gag protein and enhance packaging and infectivity. J Virol 79(12):7756–7767PubMedGoogle Scholar
  55. 55.
    Accola MA, Strack B, Gottlinger HG (2000) Efficient particle production by minimal Gag constructs which retain the carboxy-terminal domain of human immunodeficiency virus type 1 capsid-p2 and a late assembly domain. J Virol 74(12):5395–5402PubMedGoogle Scholar
  56. 56.
    Crist RM, Datta SA, Stephen AG, Soheilian F, Mirro J, Fisher RJ et al (2009) Assembly properties of human immunodeficiency virus type 1 Gag-leucine zipper chimeras: implications for retrovirus assembly. J Virol 83(5):2216–2225PubMedGoogle Scholar
  57. 57.
    Zhang Y, Qian H, Love Z, Barklis E (1998) Analysis of the assembly function of the human immunodeficiency virus type 1 gag protein nucleocapsid domain. J Virol 72(3):1782–1789PubMedGoogle Scholar
  58. 58.
    Zhang Y, Barklis E (1997) Effects of nucleocapsid mutations on human immunodeficiency virus assembly and RNA encapsidation. J Virol 71(9):6765–6776PubMedGoogle Scholar
  59. 59.
    Johnson MC, Scobie HM, Ma YM, Vogt VM (2002) Nucleic acid-independent retrovirus assembly can be driven by dimerization. J Virol 76(22):11177–11185PubMedGoogle Scholar
  60. 60.
    Certo JL, Shook BF, Yin PD, Snider JT, Hu WS (1998) Nonreciprocal pseudotyping: murine leukemia virus proteins cannot efficiently package spleen necrosis virus-based vector RNA. J Virol 72(7):5408–5413PubMedGoogle Scholar
  61. 61.
    Kaye JF, Lever AM (1998) Nonreciprocal packaging of human immunodeficiency virus type 1 and type 2 RNA: a possible role for the p2 domain of Gag in RNA encapsidation. J Virol 72(7):5877–5885PubMedGoogle Scholar
  62. 62.
    Al Shamsi IR, Al Dhaheri NS, Phillip PS, Mustafa F, Rizvi TA (2011) Reciprocal cross-packaging of primate lentiviral (HIV-1 and SIV) RNAs by heterologous non-lentiviral MPMV proteins. Virus Res 155(1):352–357PubMedGoogle Scholar
  63. 63.
    Al Dhaheri NS, Phillip PS, Ghazawi A, Ali J, Beebi E, Jaballah SA et al (2009) Cross-packaging of genetically distinct mouse and primate retroviral RNAs. Retrovirology 6:66PubMedGoogle Scholar
  64. 64.
    Browning MT, Schmidt RD, Lew KA, Rizvi TA (2001) Primate and feline lentivirus vector RNA packaging and propagation by heterologous lentivirus virions. J Virol 75(11):5129–5140PubMedGoogle Scholar
  65. 65.
    Parveen Z, Mukhtar M, Goodrich A, Acheampong E, Dornburg R, Pomerantz RJ (2004) Cross-packaging of human immunodeficiency virus type 1 vector RNA by spleen necrosis virus proteins: construction of a new generation of spleen necrosis virus-derived retroviral vectors. J Virol 78(12):6480–6488PubMedGoogle Scholar
  66. 66.
    Strappe PM, Hampton DW, Brown D, Cachon-Gonzalez B, Caldwell M, Fawcett JW et al (2005) Identification of unique reciprocal and non reciprocal cross packaging relationships between HIV-1, HIV-2 and SIV reveals an efficient SIV/HIV-2 lentiviral vector system with highly favourable features for in vivo testing and clinical usage. Retrovirology 2:55PubMedGoogle Scholar
  67. 67.
    Berkowitz RD, Ohagen A, Hoglund S, Goff SP (1995) Retroviral nucleocapsid domains mediate the specific recognition of genomic viral RNAs by chimeric Gag polyproteins during RNA packaging in vivo. J Virol 69(10):6445–6456PubMedGoogle Scholar
  68. 68.
    Zhang Y, Barklis E (1995) Nucleocapsid protein effects on the specificity of retrovirus RNA encapsidation. J Virol 69(9):5716–5722PubMedGoogle Scholar
  69. 69.
    Certo JL, Kabdulov TO, Paulson ML, Anderson JA, Hu WS (1999) The nucleocapsid domain is responsible for the ability of spleen necrosis virus (SNV) Gag polyprotein to package both SNV and murine leukemia virus RNA. J Virol 73(11):9170–9177PubMedGoogle Scholar
  70. 70.
    Dupraz P, Spahr PF (1992) Specificity of Rous sarcoma virus nucleocapsid protein in genomic RNA packaging. J Virol 66(8):4662–4670PubMedGoogle Scholar
  71. 71.
    Poon DT, Li G, Aldovini A (1998) Nucleocapsid and matrix protein contributions to selective human immunodeficiency virus type 1 genomic RNA packaging. J Virol 72(3):1983–1993PubMedGoogle Scholar
  72. 72.
    Russell RS, Roldan A, Detorio M, Hu J, Wainberg MA, Liang C (2003) Effects of a single amino acid substitution within the p2 region of human immunodeficiency virus type 1 on packaging of spliced viral RNA. J Virol 77(24):12986–12995PubMedGoogle Scholar
  73. 73.
    Russell RS, Hu J, Beriault V, Mouland AJ, Laughrea M, Kleiman L et al (2003) Sequences downstream of the 5′ splice donor site are required for both packaging and dimerization of human immunodeficiency virus type 1 RNA. J Virol 77(1):84–96PubMedGoogle Scholar
  74. 74.
    Rong L, Russell RS, Hu J, Laughrea M, Wainberg MA, Liang C (2003) Deletion of stem-loop 3 is compensated by second-site mutations within the Gag protein of human immunodeficiency virus type 1. Virology 314(1):221–228PubMedGoogle Scholar
  75. 75.
    Ristic N, Chin MP (2010) Mutations in matrix and SP1 repair the packaging specificity of a Human Immunodeficiency Virus Type 1 mutant by reducing the association of Gag with spliced viral RNA. Retrovirology 7:73PubMedGoogle Scholar
  76. 76.
    Liang C, Rong L, Laughrea M, Kleiman L, Wainberg MA (1998) Compensatory point mutations in the human immunodeficiency virus type 1 Gag region that are distal from deletion mutations in the dimerization initiation site can restore viral replication. J Virol 72(8):6629–6636PubMedGoogle Scholar
  77. 77.
    Parent LJ, Gudleski N (2011) Beyond plasma membrane targeting: role of the MA domain of Gag in retroviral genome encapsidation. J Mol Biol 410(4):553–564PubMedGoogle Scholar
  78. 78.
    Gudleski N, Flanagan JM, Ryan EP, Bewley MC, Parent LJ (2010) Directionality of nucleocytoplasmic transport of the retroviral gag protein depends on sequential binding of karyopherins and viral RNA. Proc Natl Acad Sci U S A 107(20):9358–9363PubMedGoogle Scholar
  79. 79.
    Garbitt-Hirst R, Kenney SP, Parent LJ (2009) Genetic evidence for a connection between Rous sarcoma virus gag nuclear trafficking and genomic RNA packaging. J Virol 83(13):6790–6797PubMedGoogle Scholar
  80. 80.
    Scheifele LZ, Garbitt RA, Rhoads JD, Parent LJ (2002) Nuclear entry and CRM1-dependent nuclear export of the Rous sarcoma virus Gag polyprotein. Proc Natl Acad Sci U S A 99(6):3944–3949PubMedGoogle Scholar
  81. 81.
    Garbitt RA, Albert JA, Kessler MD, Parent LJ (2001) Trans-acting inhibition of genomic RNA dimerization by Rous sarcoma virus matrix mutants. J Virol 75(1):260–268PubMedGoogle Scholar
  82. 82.
    Parent LJ, Cairns TM, Albert JA, Wilson CB, Wills JW, Craven RC (2000) RNA dimerization defect in a Rous sarcoma virus matrix mutant. J Virol 74(1):164–172PubMedGoogle Scholar
  83. 83.
    Baluyot MF, Grosse SA, Lyddon TD, Janaka SK, Johnson MC (2012) CRM1-Dependent Trafficking of Retroviral Gag Proteins Revisited. J Virol 86(8):4696–4700PubMedGoogle Scholar
  84. 84.
    Kemler I, Saenz D, Poeschla E (2012) Feline immunodeficiency virus Gag is a nuclear shuttling protein. J Virol 86(16):8402–8411PubMedGoogle Scholar
  85. 85.
    Dupont S, Sharova N, DeHoratius C, Virbasius CM, Zhu X, Bukrinskaya AG et al (1999) A novel nuclear export activity in HIV-1 matrix protein required for viral replication. Nature 402(6762):681–685PubMedGoogle Scholar
  86. 86.
    Bukrinsky MI, Haggerty S, Dempsey MP, Sharova N, Adzhubel A, Spitz L et al (1993) A nuclear localization signal within HIV-1 matrix protein that governs infection of non-dividing cells. Nature 365(6447):666–669PubMedGoogle Scholar
  87. 87.
    Grewe B, Hoffmann B, Ohs I, Blissenbach M, Brandt S, Tippler B et al (2012) Cytoplasmic utilization of human immunodeficiency virus type 1 genomic RNA is not dependent on a nuclear interaction with gag. J Virol 86(6):2990–3002PubMedGoogle Scholar
  88. 88.
    Levin JG, Rosenak MJ (1976) Synthesis of murine leukemia virus proteins associated with virions assembled in actinomycin D-treated cells: evidence for persistence of viral messenger RNA. Proc Natl Acad Sci U S A 73(4):1154–1158PubMedGoogle Scholar
  89. 89.
    Levin JG, Grimley PM, Ramseur JM, Berezesky IK (1974) Deficiency of 60 to 70S RNA in murine leukemia virus particles assembled in cells treated with actinomycin D. J Virol 14(1):152–161PubMedGoogle Scholar
  90. 90.
    Dorman N, Lever A (2000) Comparison of viral genomic RNA sorting mechanisms in human immunodeficiency virus type 1 (HIV-1), HIV-2, and Moloney murine leukemia virus. J Virol 74(23):11413–11417PubMedGoogle Scholar
  91. 91.
    Butsch M, Boris-Lawrie K (2002) Destiny of unspliced retroviral RNA: ribosome and/or virion? J Virol 76(7):3089–3094PubMedGoogle Scholar
  92. 92.
    Poon DT, Chertova EN, Ott DE (2002) Human immunodeficiency virus type 1 preferentially encapsidates genomic RNAs that encode Pr55(Gag): functional linkage between translation and RNA packaging. Virology 293(2):368–378PubMedGoogle Scholar
  93. 93.
    Liang C, Hu J, Russell RS, Wainberg MA (2002) Translation of Pr55(gag) augments packaging of human immunodeficiency virus type 1 RNA in a cis-acting manner. AIDS Res Hum Retroviruses 18(15):1117–1126PubMedGoogle Scholar
  94. 94.
    Nikolaitchik O, Rhodes TD, Ott D, Hu WS (2006) Effects of mutations in the human immunodeficiency virus type 1 Gag gene on RNA packaging and recombination. J Virol 80(10):4691–4697PubMedGoogle Scholar
  95. 95.
    Kaye JF, Lever AM (1999) Human immunodeficiency virus types 1 and 2 differ in the predominant mechanism used for selection of genomic RNA for encapsidation. J Virol 73(4):3023–3031PubMedGoogle Scholar
  96. 96.
    Ni N, Nikolaitchik OA, Dilley KA, Chen J, Galli A, Fu W et al (2011) Mechanisms of human immunodeficiency virus type 2 RNA packaging: efficient trans packaging and selection of RNA copackaging partners. J Virol 85(15):7603–7612PubMedGoogle Scholar
  97. 97.
    Clever JL, Wong ML, Parslow TG (1996) Requirements for kissing-loop-mediated dimerization of human immunodeficiency virus RNA. J Virol 70(9):5902–5908PubMedGoogle Scholar
  98. 98.
    Mujeeb A, Clever JL, Billeci TM, James TL, Parslow TG (1998) Structure of the dimer initiation complex of HIV-1 genomic RNA. Nat Struct Biol 5(6):432–436PubMedGoogle Scholar
  99. 99.
    McBride MS, Panganiban AT (1997) Position dependence of functional hairpins important for human immunodeficiency virus type 1 RNA encapsidation in vivo. J Virol 71(3):2050–2058PubMedGoogle Scholar
  100. 100.
    McBride MS, Schwartz MD, Panganiban AT (1997) Efficient encapsidation of human immunodeficiency virus type 1 vectors and further characterization of cis elements required for encapsidation. J Virol 71(6):4544–4554PubMedGoogle Scholar
  101. 101.
    Li X, Liang C, Quan Y, Chandok R, Laughrea M, Parniak MA et al (1997) Identification of sequences downstream of the primer binding site that are important for efficient replication of human immunodeficiency virus type 1. J Virol 71(8):6003–6010PubMedGoogle Scholar
  102. 102.
    Heng X, Kharytonchyk S, Garcia EL, Lu K, Divakaruni SS, LaCotti C et al (2012) Identification of a minimal region of the HIV-1 5′-leader required for RNA dimerization, NC binding, and packaging. J Mol Biol 417(3):224–239PubMedGoogle Scholar
  103. 103.
    Das AT, Klaver B, Klasens BI, van Wamel JL, Berkhout B (1997) A conserved hairpin motif in the R-U5 region of the human immunodeficiency virus type 1 RNA genome is essential for replication. J Virol 71(3):2346–2356PubMedGoogle Scholar
  104. 104.
    Helga-Maria C, Hammarskjold ML, Rekosh D (1999) An intact TAR element and cytoplasmic localization are necessary for efficient packaging of human immunodeficiency virus type 1 genomic RNA. J Virol 73(5):4127–4135PubMedGoogle Scholar
  105. 105.
    Clever JL, Eckstein DA, Parslow TG (1999) Genetic dissociation of the encapsidation and reverse transcription functions in the 5′ R region of human immunodeficiency virus type 1. J Virol 73(1):101–109PubMedGoogle Scholar
  106. 106.
    Pallesen J (2011) Structure of the HIV-1 5′ untranslated region dimer alone and in complex with gold nanocolloids: support of a TAR-TAR-containing 5′ dimer linkage site (DLS) and a 3′ DIS-DIS-containing DLS. Biochemistry 50(28):6170–6177PubMedGoogle Scholar
  107. 107.
    Das AT, Harwig A, Vrolijk MM, Berkhout B (2007) The TAR hairpin of human immunodeficiency virus type 1 can be deleted when not required for Tat-mediated activation of transcription. J Virol 81(14):7742–7748PubMedGoogle Scholar
  108. 108.
    Malim MH, Hauber J, Le SY, Maizel JV, Cullen BR (1989) The HIV-1 rev trans-activator acts through a structured target sequence to activate nuclear export of unspliced viral mRNA. Nature 338(6212):254–257PubMedGoogle Scholar
  109. 109.
    Malim MH, Tiley LS, McCarn DF, Rusche JR, Hauber J, Cullen BR (1990) HIV-1 structural gene expression requires binding of the Rev trans-activator to its RNA target sequence. Cell 60(4):675–683PubMedGoogle Scholar
  110. 110.
    Kjems J, Brown M, Chang DD, Sharp PA (1991) Structural analysis of the interaction between the human immunodeficiency virus Rev protein and the Rev response element. Proc Natl Acad Sci U S A 88(3):683–687PubMedGoogle Scholar
  111. 111.
    Charpentier B, Stutz F, Rosbash M (1997) A dynamic in vivo view of the HIV-I Rev-RRE interaction. J Mol Biol 266(5):950–962PubMedGoogle Scholar
  112. 112.
    Lesnik EA, Sampath R, Ecker DJ (2002) Rev response elements (RRE) in lentiviruses: an RNAMotif algorithm-based strategy for RRE prediction. Med Res Rev 22(6):617–636PubMedGoogle Scholar
  113. 113.
    Mann DA, Mikaelian I, Zemmel RW, Green SM, Lowe AD, Kimura T et al (1994) A molecular rheostat. Co-operative rev binding to stem I of the rev-response element modulates human immunodeficiency virus type-1 late gene expression. J Mol Biol 241(2):193–207PubMedGoogle Scholar
  114. 114.
    Neville M, Stutz F, Lee L, Davis LI, Rosbash M (1997) The importin-beta family member Crm1p bridges the interaction between Rev and the nuclear pore complex during nuclear export. Curr Biol 7(10):767–775PubMedGoogle Scholar
  115. 115.
    Cochrane AW, Chen CH, Rosen CA (1990) Specific interaction of the human immunodeficiency virus Rev protein with a structured region in the env mRNA. Proc Natl Acad Sci U S A 87(3):1198–1202PubMedGoogle Scholar
  116. 116.
    Fornerod M, Ohno M, Yoshida M, Mattaj IW (1997) CRM1 is an export receptor for leucine-rich nuclear export signals. Cell 90(6):1051–1060PubMedGoogle Scholar
  117. 117.
    Daugherty MD, Liu B, Frankel AD (2010) Structural basis for cooperative RNA binding and export complex assembly by HIV Rev. Nat Struct Mol Biol 17(11):1337–1342PubMedGoogle Scholar
  118. 118.
    Daugherty MD, Booth DS, Jayaraman B, Cheng Y, Frankel AD (2010) HIV Rev response element (RRE) directs assembly of the Rev homooligomer into discrete asymmetric complexes. Proc Natl Acad Sci U S A 107(28):12481–12486PubMedGoogle Scholar
  119. 119.
    McLaren M, Marsh K, Cochrane A (2008) Modulating HIV-1 RNA processing and utilization. Front Biosci 13:5693–5707PubMedGoogle Scholar
  120. 120.
    Brandt S, Blissenbach M, Grewe B, Konietzny R, Grunwald T, Uberla K (2007) Rev proteins of human and simian immunodeficiency virus enhance RNA encapsidation. PLoS Pathog 3(4):e54PubMedGoogle Scholar
  121. 121.
    Bray M, Prasad S, Dubay JW, Hunter E, Jeang KT, Rekosh D et al (1994) A small element from the Mason-Pfizer monkey virus genome makes human immunodeficiency virus type 1 expression and replication Rev-independent. Proc Natl Acad Sci U S A 91(4):1256–1260PubMedGoogle Scholar
  122. 122.
    Moore MD, Nikolaitchik OA, Chen J, Hammarskjold ML, Rekosh D, Hu WS (2009) Probing the HIV-1 genomic RNA trafficking pathway and dimerization by genetic recombination and single virion analyses. PLoS Pathog 5(10):e1000627PubMedGoogle Scholar
  123. 123.
    Braun IC, Rohrbach E, Schmitt C, Izaurralde E (1999) TAP binds to the constitutive transport element (CTE) through a novel RNA-binding motif that is sufficient to promote CTE-dependent RNA export from the nucleus. EMBO J 18(7):1953–1965PubMedGoogle Scholar
  124. 124.
    Gruter P, Tabernero C, von Kobbe C, Schmitt C, Saavedra C, Bachi A et al (1998) TAP, the human homolog of Mex67p, mediates CTE-dependent RNA export from the nucleus. Mol Cell 1(5):649–659PubMedGoogle Scholar
  125. 125.
    Kang Y, Cullen BR (1999) The human Tap protein is a nuclear mRNA export factor that contains novel RNA-binding and nucleocytoplasmic transport sequences. Genes Dev 13(9):1126–1139PubMedGoogle Scholar
  126. 126.
    Wiegand HL, Coburn GA, Zeng Y, Kang Y, Bogerd HP, Cullen BR (2002) Formation of Tap/NXT1 heterodimers activates Tap-dependent nuclear mRNA export by enhancing recruitment to nuclear pore complexes. Mol Cell Biol 22(1):245–256PubMedGoogle Scholar
  127. 127.
    Blissenbach M, Grewe B, Hoffmann B, Brandt S, Uberla K (2010) Nuclear RNA export and packaging functions of HIV-1 Rev revisited. J Virol 84(13):6598–6604PubMedGoogle Scholar
  128. 128.
    Fu W, Gorelick RJ, Rein A (1994) Characterization of human immunodeficiency virus type 1 dimeric RNA from wild-type and protease-defective virions. J Virol 68(8):5013–5018PubMedGoogle Scholar
  129. 129.
    Fu W, Rein A (1993) Maturation of dimeric viral RNA of Moloney murine leukemia virus. J Virol 67(9):5443–5449PubMedGoogle Scholar
  130. 130.
    Moore MD, Fu W, Nikolaitchik O, Chen J, Ptak RG, Hu WS (2007) Dimer initiation signal of human immunodeficiency virus type 1: its role in partner selection during RNA copackaging and its effects on recombination. J Virol 81(8):4002–4011PubMedGoogle Scholar
  131. 131.
    Muriaux D, Fosse P, Paoletti J (1996) A kissing complex together with a stable dimer is involved in the HIV-1Lai RNA dimerization process in vitro. Biochemistry 35(15):5075–5082PubMedGoogle Scholar
  132. 132.
    Paillart JC, Berthoux L, Ottmann M, Darlix JL, Marquet R, Ehresmann B et al (1996) A dual role of the putative RNA dimerization initiation site of human immunodeficiency virus type 1 in genomic RNA packaging and proviral DNA synthesis. J Virol 70(12):8348–8354PubMedGoogle Scholar
  133. 133.
    Skripkin E, Paillart JC, Marquet R, Ehresmann B, Ehresmann C (1994) Identification of the primary site of the human immunodeficiency virus type 1 RNA dimerization in vitro. Proc Natl Acad Sci U S A 91(11):4945–4949PubMedGoogle Scholar
  134. 134.
    Berkhout B, van Wamel JL (1996) Role of the DIS hairpin in replication of human immunodeficiency virus type 1. J Virol 70(10):6723–6732PubMedGoogle Scholar
  135. 135.
    Laughrea M, Jette L (1996) Kissing-loop model of HIV-1 genome dimerization: HIV-1 RNAs can assume alternative dimeric forms, and all sequences upstream or downstream of hairpin 248–271 are dispensable for dimer formation. Biochemistry 35(5):1589–1598PubMedGoogle Scholar
  136. 136.
    St Louis DC, Gotte D, Sanders-Buell E, Ritchey DW, Salminen MO, Carr JK et al (1998) Infectious molecular clones with the nonhomologous dimer initiation sequences found in different subtypes of human immunodeficiency virus type 1 can recombine and initiate a spreading infection in vitro. J Virol 72(5):3991–3998PubMedGoogle Scholar
  137. 137.
    Hussein IT, Ni N, Galli A, Chen J, Moore MD, Hu WS (2010) Delineation of the preferences and requirements of the human immunodeficiency virus type 1 dimerization initiation signal by using an in vivo cell-based selection approach. J Virol 84(13):6866–6875PubMedGoogle Scholar
  138. 138.
    Sakuragi J, Sakuragi S, Ohishi M, Shioda T (2010) Direct correlation between genome dimerization and recombination efficiency of HIV-1. Microbes Infect 12(12–13):1002–1011PubMedGoogle Scholar
  139. 139.
    Chin MP, Rhodes TD, Chen J, Fu W, Hu WS (2005) Identification of a major restriction in HIV-1 intersubtype recombination. Proc Natl Acad Sci U S A 102(25):9002–9007PubMedGoogle Scholar
  140. 140.
    Chin MP, Lee SK, Chen J, Nikolaitchik OA, Powell DA, Fivash MJ Jr et al (2008) Long-range recombination gradient between HIV-1 subtypes B and C variants caused by sequence differences in the dimerization initiation signal region. J Mol Biol 377(5):1324–1333PubMedGoogle Scholar
  141. 141.
    Chin MP, Chen J, Nikolaitchik OA, Hu WS (2007) Molecular determinants of HIV-1 intersubtype recombination potential. Virology 363(2):437–446PubMedGoogle Scholar
  142. 142.
    Nikolaitchik OA, Galli A, Moore MD, Pathak VK, Hu WS (2011) Multiple barriers to recombination between divergent HIV-1 variants revealed by a dual-marker recombination assay. J Mol Biol 407(4):521–531PubMedGoogle Scholar
  143. 143.
    Sakuragi J, Ueda S, Iwamoto A, Shioda T (2003) Possible role of dimerization in human immunodeficiency virus type 1 genome RNA packaging. J Virol 77(7):4060–4069PubMedGoogle Scholar
  144. 144.
    Hoglund S, Ohagen A, Goncalves J, Panganiban AT, Gabuzda D (1997) Ultrastructure of HIV-1 genomic RNA. Virology 233(2):271–279PubMedGoogle Scholar
  145. 145.
    D’Souza V, Summers MF (2004) Structural basis for packaging the dimeric genome of Moloney murine leukaemia virus. Nature 431(7008):586–590PubMedGoogle Scholar
  146. 146.
    Gherghe C, Lombo T, Leonard CW, Datta SA, Bess JW Jr, Gorelick RJ et al (2010) Definition of a high-affinity Gag recognition structure mediating packaging of a retroviral RNA genome. Proc Natl Acad Sci U S A 107(45):19248–19253PubMedGoogle Scholar
  147. 147.
    Miyazaki Y, Garcia EL, King SR, Iyalla K, Loeliger K, Starck P et al (2010) An RNA structural switch regulates diploid genome packaging by Moloney murine leukemia virus. J Mol Biol 396(1):141–152PubMedGoogle Scholar
  148. 148.
    Gherghe C, Leonard CW, Gorelick RJ, Weeks KM (2010) Secondary structure of the mature ex virio Moloney murine leukemia virus genomic RNA dimerization domain. J Virol 84(2):898–906PubMedGoogle Scholar
  149. 149.
    Badorrek CS, Weeks KM (2006) Architecture of a gamma retroviral genomic RNA dimer. Biochemistry 45(42):12664–12672PubMedGoogle Scholar
  150. 150.
    D’Souza V, Dey A, Habib D, Summers MF (2004) NMR structure of the 101-nucleotide core encapsidation signal of the Moloney murine leukemia virus. J Mol Biol 337(2):427–442PubMedGoogle Scholar
  151. 151.
    Ooms M, Huthoff H, Russell R, Liang C, Berkhout B (2004) A riboswitch regulates RNA dimerization and packaging in human immunodeficiency virus type 1 virions. J Virol 78(19):10814–10819PubMedGoogle Scholar
  152. 152.
    Abbink TE, Ooms M, Haasnoot PC, Berkhout B (2005) The HIV-1 leader RNA conformational switch regulates RNA dimerization but does not regulate mRNA translation. Biochemistry 44(25):9058–9066PubMedGoogle Scholar
  153. 153.
    Poole E, Strappe P, Mok HP, Hicks R, Lever AM (2005) HIV-1 Gag-RNA interaction occurs at a perinuclear/centrosomal site; analysis by confocal microscopy and FRET. Traffic 6(9):741–755PubMedGoogle Scholar
  154. 154.
    Kemler I, Meehan A, Poeschla EM (2010) Live-cell coimaging of the genomic RNAs and Gag proteins of two lentiviruses. J Virol 84(13):6352–6366PubMedGoogle Scholar
  155. 155.
    Jouvenet N, Neil SJ, Bess C, Johnson MC, Virgen CA, Simon SM et al (2006) Plasma membrane is the site of productive HIV-1 particle assembly. PLoS Biol 4(12):e435PubMedGoogle Scholar
  156. 156.
    Ono A (2010) HIV-1 assembly at the plasma membrane. Vaccine 28(Suppl 2):B55–B59PubMedGoogle Scholar
  157. 157.
    Jouvenet N, Bieniasz PD, Simon SM (2008) Imaging the biogenesis of individual HIV-1 virions in live cells. Nature 454(7201):236–240PubMedGoogle Scholar
  158. 158.
    Ivanchenko S, Godinez WJ, Lampe M, Krausslich HG, Eils R, Rohr K et al (2009) Dynamics of HIV-1 assembly and release. PLoS Pathog 5(11):e1000652PubMedGoogle Scholar
  159. 159.
    Jouvenet N, Simon SM, Bieniasz PD (2009) Imaging the interaction of HIV-1 genomes and Gag during assembly of individual viral particles. Proc Natl Acad Sci U S A 106(45):19114–19119PubMedGoogle Scholar
  160. 160.
    Kutluay SB, Bieniasz PD (2010) Analysis of the initiating events in HIV-1 particle assembly and genome packaging. PLoS Pathog 6(11):e1001200PubMedGoogle Scholar
  161. 161.
    Molle D, Segura-Morales C, Camus G, Berlioz-Torrent C, Kjems J, Basyuk E et al (2009) Endosomal trafficking of HIV-1 gag and genomic RNAs regulates viral egress. J Biol Chem 284(29):19727–19743PubMedGoogle Scholar
  162. 162.
    Lehmann M, Milev MP, Abrahamyan L, Yao XJ, Pante N, Mouland AJ (2009) Intracellular transport of human immunodeficiency virus type 1 genomic RNA and viral production are dependent on dynein motor function and late endosome positioning. J Biol Chem 284(21):14572–14585PubMedGoogle Scholar
  163. 163.
    Ono A (2009) HIV-1 assembly at the plasma membrane: Gag trafficking and localization. Future Virol 4(3):241–257PubMedGoogle Scholar
  164. 164.
    Beriault V, Clement JF, Levesque K, Lebel C, Yong X, Chabot B et al (2004) A late role for the association of hnRNP A2 with the HIV-1 hnRNP A2 response elements in genomic RNA, Gag, and Vpr localization. J Biol Chem 279(42):44141–44153PubMedGoogle Scholar
  165. 165.
    Mouland AJ, Xu H, Cui H, Krueger W, Munro TP, Prasol M et al (2001) RNA trafficking signals in human immunodeficiency virus type 1. Mol Cell Biol 21(6):2133–2143PubMedGoogle Scholar
  166. 166.
    Levesque K, Halvorsen M, Abrahamyan L, Chatel-Chaix L, Poupon V, Gordon H et al (2006) Trafficking of HIV-1 RNA is mediated by heterogeneous nuclear ribonucleoprotein A2 expression and impacts on viral assembly. Traffic 7(9):1177–1193PubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2013

Authors and Affiliations

  • Jianbo Chen
    • 1
  • Olga A. Nikolaitchik
    • 1
  • Kari A. Dilley
    • 1
  • Wei-Shau Hu
    • 2
  1. 1.HIV Drug Resistance Program, Viral Recombination SectionNational Cancer InstituteFrederickUSA
  2. 2.HIV Drug Resistance ProgramNational Cancer InstituteFrederickUSA

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