Abstract
Unlike many animal viruses, infection by retroviruses generally does not lead to cessation of host RNA synthesis. Despite the high levels of host RNA in infected cells, the vast majority of retroviral particles contain a precise genomic complex consisting of two molecules of genomic RNA, rather than cellular or subgenomic viral mRNAs. Thus, the retroviral genome must be selected for encapsidation against a high background of cellular RNAs. It is therefore surprising that the retroviral genome is structurally similar to that of cellular mRNA. For instance, both molecules contain a 5′ m7 G cap and several hundred A residues at the 3′ terminus (reviewed in Coffin 1984a, 1985). Viral subgenomic mRNAs are even more similar to genomic RNA. The ability of the retroviral particle to choose correctly genomic RNA from the vast excess of heterologous molecules implies that specific sequences are present within the genome which direct the efficient encapsidation of the correct RNAs. Analysis of spontaneous and engineered mutants of both avian and murine retroviruses has in fact revealed that cis-acting sequences are involved and are present in the retroviral genome.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
Adam MA, Miller AD (1988) Identification of a signal in a murine retrovirus that is sufficient for packaging of non-retroviral RNA into virions. J Virol 62: 3802–3806
Adkins B, Hunter T (1981) Identification of a packaged cellular mRNA in virions of Rous sarcoma virus. J Virol 39: 471–481
Armentano D, Yu S-F, Kantoff PW, von Ruden T, Anderson WF, Gilboa E (1987) Effect of internal viral sequences on the utility of retroviral vectors. J Virol 61: 1647–1650
Baltimore D (1985) Retroviruses and retrotransposons: the role of reverse transcriptase in shaping the eukaryotic genome. Cell 40: 481–482
Bender MA, Palmer TD, Gelinas RE, Miller AD (1987) Evidence that the packaging signal of Moloney murine leukemia virus extends into the gag region. J Virol 61: 1639–1646
Besmer P, Olshevsky D, Baltimore D, Dolberg D, Fan H (1979) Virus-like 30S RNA in mouse cells. J Virol 29: 1168–1176
Biczysko W, Pienkowski M, Solter D, Koprowski H (1973) Virus particles in early mouse embryos. JNCI 51: 1041–1959
Biegalke B, Linial M (1987) Retention or loss of v-mil sequences after propagation of MH2 virus in vivo or in vitro. J Virol 61: 1949–1956
Bister K, Jansen HW (1986) Oncogenes in retroviruses and cells: biochemistry and molecular genetics. Adv Cancer Res 47: 99–188
Bosselman RA, Hsu R-Y, Bruszewski J, Hu S, Martin F, Nicholson M (1987) Replication-defective chimeric helper proviruses and factors affecting generation of competent virus: expression of Moloney murine leukemia virus structural genes via the metallothionein promoter. Mol Cell Biol 7: 1797–1806
Canaani E, von der Helm K, Duesberg P (1973) Evidence for 30–40S RNA as precursor of the 60–70S RNA of Rous sarcoma virus. Proc Natl Acad Sci USA 70: 401–405
Chen P-J, Cywinski A, Taylor JM (1985) Reverse transcription of 7S-L RNA by an avian retrovirus. J Virol 54: 278–284
Cheung K-S, Smith RE, Stone MP, Joklik WK (1972) Comparison of immature (rapid) and mature Rous sarcoma virus particles. Virology 50: 851–864
Coffin JM (1979) Structure, replication and recombination of retrovirus genomes. J Gen Virol 42: 1–26
Coffin JM (1984a) Structure of the retroviral genome. In: Weiss R, Teich N, Varmus H, Coffin J (eds) 2nd edn, Part 1, Cold Spring Harbor Laboratory, Cold Spring Harbor, pp 261–368
Coffin JM (1984b) Endogenous viruses. In: Weiss R, Teich N, Varmus H, Coffin J (eds) RNA tumor viruses. 2nd edn, Part 2. Cold Spring Harbor Laboratory, Cold Spring Harbor, pp 1110–1202
Coffin JM (1985) Genome structure. In: Weiss R, Teich N, Varmus H, Coffin J (eds) RNA tumor viruses. 2nd edn, Part 2. Cold Spring Harbor Laboratory, Cold Spring Harbor, pp 17–74
Cone RD, Mulligan RC (1984) High-efficiency gene transfer into mammalian cells: generation of helper-free recombinant retrovirus with broad mammalian host range. Proc Natl Acad Sci USA 81:6349–6353
Copeland NG, Hutchison KW, Jenkins NA (1983) Excision of the DBA ecotropic provirus in dilute coat-color revertants of mice occurs by homologous recombination involving the viral LTRs. Cell 33: 379–387
Covey SN, Turner DS (1986) Hairpin DNAs of cauliflower mosaic virus generated by reverse transcription in vivo. EMBO J 5: 2763–2768
DeGudicibus SJ, Gentile B, Bhatt RS, Poonian MS, Stacey DW (1986) Studies of retroviral packaging. In: Celis JE, Graessmann A, Loyter A (eds) Microinjection and organelle transplantation techniques. Academic, London, pp 59–65
Dickson C, Eisenman R, Fan H, Hunter E, Teich N (1984) Protein biosynthesis and assembly. In: Weiss R, Teich N, Varmus H, Coffin J (eds) RNA tumor viruses 2nd edn, Part I. Cold Spring Harbor Laboratory, Cold Spring Harbor, pp 785–998
Dornburg R, Temin HM (1988) Retroviral vector system for the study of cDNA gene formation. Mol Cell Biol 8: 2329–2334
Embretson JE, Temin HM (1987) Lack of competition results in efficient packaging of heterologous murine retroviral RNAs and reticuloendotheliosis virus encapsidation-minus RNAs by the reticuloendotheliosis virus helper cell line. J Virol 61: 2675–2683
Fu X, Phillips N, Jentoft J, Tuazon PT, Traugh JA, Leis J (1985) Site-specific phosphorylation of avian retrovirus nucleocapsid protein pp 12 regulates binding to RNA. J Biol Chem 260: 9941–9947
Fu X, Katz RA, Skalka AM, Leis J (1988) Site-directed mutagenesis of the avian retrovirus nucleocapsid protein pp 12: mutation which affects RNA binding in vitro blocks viral replication. J Biol Chem 263: 2134–2139
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: 146–161
Garfinkel DJ, Boeke JD, Fink GR (1985) Ty element transposition: reverse transcriptase and viruslike particles. Cell 42: 507–517
Geryk J, Pichrtova J, Guntaka RV, Gowda S, Svoboda J (1986) Characterization of transforming viruses rescued from a hamster tumour cell line harbouring the v-src gene flanked by long terminal repeats. J Gen Virol 67: 2395–2404
Gerwin BI, Levin JG (1977) Interactions of murine leukemia virus core components: characterization of reverse transcriptase packaged in the absence of 70S genomic RNA. J Virol 24: 478–488
Goldfarb MP, Weinberg RA (1981) Generation of novel, biologically active Harvey sarcoma viruses via apparent illegitimate recombination. J Virol 38: 136–150
Gorelick RJ, Henderson LE, Hanser JP, 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 Nat Acad Sci USA 85: 8420–8424
Heidmann T, Heidmann O, Nicolas J-F (1988) An indicator gene to demonstrate intracellular transposition of defective retroviruses. Proc Natl Acad Sci USA 85: 2219–2223
Herman SA, Coffin JM (1986) Differential transcription from the long terminal repeats of integrated avian leukosis virus. J Virol 60: 497–505
Herman SA, Coffin JM (1987) Efficient packaging of readthrough RNA in ALV: implications for oncogene transduction. Science 236: 845–848
Huang TTF, Calarco PG (1981) Evidence of cell surface expression of intracisternal A particle-associated antigens during early mouse development. Dev Biol 82: 388–392
Hunter E (1978) The mechanism for genetic recombination in the avian retroviruses. Curr Top Microbiol Immunol 79: 295–309
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 USA 71: 1154–1158
Jagadeeswaran P, Forget BG, Weissman SM (1981) Short interspersed repetitive DNA elements in eukaryotes: transposable NA elements generated by reverse transcription of RNA pol III transcripts? Cell 26: 141–142
Junghans RP, Boone LR, Skalka AM (1982) Retroviral DNA H structures: displacement-assimilation model of recombination. Cell 30: 53–62
Katz RA, Terry RW, Skalka AM (1986) A conserved cis-acting sequence in the 5′ leader of avian sarcoma virus RNA is required for packaging. J Virol 59: 163–167
Kawai S, Koyama T (1984) Characterization of a Rous sarcoma virus mutant defective in packaging its own genomic RNA: biological properties of mutant TK15 and mutant-induced transformants. J Virol 51: 147–153
Kiessling A, Crowell R, Connell R (1987) Sperm-associated retrovirus in the mouse epididymus. Proc Natl Acad Sci 84: 8667–8671
Koyama T, Harada F, Kawai S (1984) Characterization of a Rous sarcoma virus mutant defective in packaging its own genomic RNA: biochemical properties of mutant TK15 and mutant-induced‘transformants’. J Virol 51: 154–162
Leis J, Baltimore D, Bishop JM, Coffin J, Fleissner E, Goff SP, Oroszlan S, Robinson H, Skalka AM, Temin HM, Vogt VM (1988) Standardized and simplified nomenclature for proteins common to all retroviruses. J Virol 62: 1808–1809
Lever A, Gottlinger H, Haseltine W and Sodroski J (1989) Identification of a sequence required for efficient packaging of human immunodeficiency virus type 1 RNA into virions. J Vir 63: 4085–4087
Levin JG, Rosenak MJ (1976) Synthesis of murine leukemia virus proteins associated with virions assemble in actinomycin D-treated cells: evidence for persistence of viral messenger RNA. Proc Natl Acad Sci USA 73: 1154–1158
Levin JG, Seidman JG (1979) Selective packaging of host tRNAs by murine leukemia virus particles does not require genomic RNA. J Virol 29: 328–335
Levin JG, Grimley PM, Ramseur JM, Berezesky IK (1974) Deficiency on 60 to 70S RNA in murine leukemia virus particles assembled in cells treated with Actinomycin D. J Virol 14: 152–161
Linial M (1981) Transfer of defective avian tumor virus genomes by a Rous sarcoma virus RNA packaging mutant. J Virol 38: 380–382
Linial M (1987) Creation of a processed pseudogene by retroviral infection. Cell 49: 93–102
Linial M, Blair D (1984) Genetics of Retroviruses. In: Weiss R, Teich N, Varmus H, Coffin J (eds) RNA tumor viruses. Cold Spring Harbor Laboratory, Cold Spring Harbor, pp 650–783
Linial M, Medeiros E, Hayward WS (1978) An avian oncovirus mutant (SE21Qlb) deficient in genomic RNA: biological and biochemical characterization. Cell 15: 1371–1381
Mann R, Baltimore D (1985) Varying the position of a retrovirus packaging sequence results in the encapsidation of both unspliced RNAs. J Virol 54: 401–407
Mann R, Mulligan RC, Baltimore D (1983) Construction of a retrovirus packaging mutant and its use to produce helper-free defective retrovirus. Cell 33: 153–159
Markowitz D, Goff S, Bank A (1988) A safe packaging line for gene transfer: separating viral genes on two different plasmids. J Virol 62: 1120–1124
Martin P, Henry C, Ferre F, Bechade C, Begue A, Calothy G, Debuire B, Stehelin D, Saule S (1986) Characterization of a myc-containing avian retrovirus generated by the propagation of an MH2 viral subgenomic RNA. J Virol 57: 1191–1194
Meric C, Darlix JL, Spahr PF (1984) It is Rous sarcoma virus p12 and not p19 that binds tightly to Rous sarcoma virus RNA. J Mol Biol 173: 531–538
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 Vir 63: 1558–1568
Meric C, Spahr P-F (1986) Rous sarcoma virus nucleic acid-binding protein p12 is necessary for viral 70S RNA dimer formation and packaging. J Virol 60: 450–459
Miller AD, Buttimore C (1986) Redesign of retrovirus packaging cell lines to avoid recombination to helper virus production. Mol Cell Biol 6: 2895–2902
Miller AD, Verma IM (1984) Two base changes restore infectivity to a noninfectious molecular clone of Moloney murine leukemia virus (pMLV-1). J Virol 49: 214–222
Miller AD, Law MF, Verma IM (1985) Generation of helper-free amphotropic retroviruses that transduce a dominant-acting methotrexate-resistant DHFR gene. Mol Cell Biol 5: 431–437
Miller AD, Trauber DR, Buttimore C (1986) Factors involved in the production of helper virus-free retrovirus vectors. Somatic Cell Mol Genet 12: 175–183
Murphy J, Goff SP Construction and analysis of deletion mutations in the U5 region of Moloney murine leukemia virus: effects on RNA packaging and reverse transcription. J Vir 63: 319–327
Nishizawa M, Koyama T, Kawai S (1985) Unusual feature of the leader sequence of Rous sarcoma virus packaging mutant TK15. J Virol 55: 881–885
Nishizawa M, Koyama T, Kawai S (1987) Frequent segregation of more defective variants from a Rous sarcoma virus packaging mutant TK15. J Virol 61: 3208–3213
Norton PA, Coffin JM (1985) Bacterial β-galactosidase as a marker of Rous sarcoma virus gene expression and replication. Mol Cell Biol 5: 281–290
Patschinsky T, Jansen HW, Blocker H, Frank R, Bister K (1986) Structure and transforming function of transduced mutant alleles of the chicken c-myc gene. J Virol 59: 341–353
Peters GG, Hu J (1980) Reverse transcriptase as the major determinant for selected packaging of tRNAs into avian sarcoma virus particles. J Virol 36: 692–700
Pugatsch T, Stacey DW (1983) Identification of a sequence likely to be required for avian retroviral packaging. Virology 128: 505–511
Rodland KD, Brown AMC, Magun B (1987) Individual mouse VL30 elements transferred to rat cells by viral pseudotypes retain their responsiveness to activators of protein kinase C. Mol Cell Biol 7: 2296–2298
Sawyer RC, Hanafusa H (1979) Comparison of the small RNAs of polymerase-deficient and polymerase-positive Rous sarcoma virus and another species of avian retrovirus. J Virol 29: 863–871
Schwartzberg P, Colicelli J, Goff SP (1983) Deletion mutants of Moloney murine leukemia virus which lack glycosylated gag protein are replication competent. J Virol 46: 538–546
Scolnick EM, Vass WC, Howk RS, Duesberg PH (1979) Defective retrovirus-like 30S RNA species of rat and mouse cells are infectious if packaged by type C helper virus. J Virol 29: 964–972
Shank PR, Linial M (1980) Avian oncovirus mutant (SE21Q1b) deficient in genomic RNA: characterization of a deletion in the provirus. J Virol 36: 450–456
Sherwin SA, Rapp UR, Benveniste RE, Sen A, Todaro GJ (1978) Rescue of endogenous 30S retroviral sequences from mouse cells by baboon type C virus. J Virol 26: 257–264
Shimotohno K, Mizutani S, Temin HM (1980) Sequence of retrovirus provirus resembles that of bacterial transposable elements. Nature 285: 550–554
Shinnick TM, Lerner RA, Sutcliffe JG (1981) Nucleotide sequence of Moloney murine leukemia virus. Nature 293: 543–548
Sorge JD, Ricci W, Hughes SH (1983) cis-Acting RNA packaging locus in the 115-nucleotide direct repeat of Rous sarcoma virus. J Virol 48: 667–675
Sorge JD, Wright D, Erdman VD, Cutting AE (1984) Amphotropic retrovirus vector system for human cell gene transfer. Mol Cell Biol 4: 1730–1737
Stoker AW, Bissell MJ (1988) Development of avian sarcoma and leukosis virus-based vector-packaging cell lines. J Virol 62: 1008–1015
Stoltzfus CM, Kuhnert LK (1979) Evidence for the identity of shared 5′-terminal sequences between genomic RNA and subgenomic mRNAs of B77 avian sarcoma virus. J Virol 32: 536–545
Svoboda J, Dvorak M, Guntaka R, Geryk J (1986) Transmission of (LTR, v-src, LTR) without recombination with a helper virus. Virology 153: 314–317
Taylor JM, Cywinski A (1984) A defective retrovirus particle (SE21Q1b) packages and reverse transcribes cellular RNA, utilizing tRNA-like primers. J Virol 51: 267–271
Temin H (1985) Reverse transcription in the eukaryotic genome: retroviruses, pararetroviruses, retrotransposons and retranscripts. Mol Biol Evol 2: 455–468
Ullu E, Murphy S, Melli M (1982) Human 7SL RNA consists of a 140 nucleotide middle-repetitive sequence inserted in an Alu sequence. Cell 29: 195–202
Van Arsdell SW, Denison RA, Bernstein LB, Weiner AM Manser T, Gesteland RF (1981) Direct repeats flank three small nuclear RNA pseudogenes in the human genome. Cell 26: 11–17
Varmus H, Swanstrom R (1984) Replication of Retroviruses. In: Weiss R, Teich N, Varmus H, Coffin J (eds) RNA tumor viruses. Cold Spring Harbor Laboratory, Cold Spring Harbor, pp 369–512
Voynow S, Coffin JM (1985) Truncated gag-related proteins are produced by large deletion mutants of Rous sarcoma virus and form virus particles. J Virol 55: 79–85
Walter P, Blobel G (1982) Signal recognition particle contains a 7S RNA essential for protein translocation across the endoplasmic reticulum. Nature 288: 691–698
Wang L-H, Stacey DW (1982) Participation of subgenomic retroviral mRNAs in recombination. J Virol 41: 919–930
Watanabe S, Temin HM (1979) Encapsidation sequences for spleen necrosis virus, an avian retrovirus, are between the 5′ long terminal repeat and the start of the gag gene. Proc Natl Acad Sci USA 79: 5986–5990
Watanabe S, Temin HM (1983) Construction of a helper cell line for avian reticuloendotheliosis virus cloning vectors. Mol Cell Biol 3: 2241–2249
Weiner AM, Deininger PL, Efstratiadis A (1986) Nonviral retroposons: genes, pseudogenes, and transposable elements generated by the reverse flow of genetic information. Annu Rev Biochem 55: 631–661
Weiss R (1984) Experimental biology and assay of RNA tumor viruses. In: Weiss R, Teich N, Varmus H, Coffin J (eds) RNA tumor viruses. Cold Spring Harbor Laboratory, Cold Spring Harbor, pp 209–260
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1990 Springer-Verlag Berlin · Heidelberg
About this paper
Cite this paper
Linial, M.L., Miller, A.D. (1990). Retroviral RNA Packaging: Sequence Requirements and Implications. In: Swanstrom, R., Vogt, P.K. (eds) Retroviruses. Current Topics in Microbiology and Immunology, vol 157. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-75218-6_5
Download citation
DOI: https://doi.org/10.1007/978-3-642-75218-6_5
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-75220-9
Online ISBN: 978-3-642-75218-6
eBook Packages: Springer Book Archive