Skip to main content
PMC home page
Springer Nature - PMC COVID-19 Collection logoLink to Springer Nature - PMC COVID-19 Collection
. 1992;48(2):201–215. doi: 10.1007/BF01923512

The role of proteolytic processing in the morphogenesis of virus particles

C U T Hellen 1, E Wimmer 1
PMCID: PMC7087542  PMID: 1740191

Abstract

Proteinases are encoded by many RNA viruses, all retroviruses and several DNA viruses. They play essential roles at various stages in viral replication, including the coordinated assembly and maturation of virions. Most of these enzymes belong to one of three (Ser, Cys or Asp) of the four major classes of proteinases, and have highly substrate-selective and cleavage specific activities. They can be thought of as playing one of two general roles in viral morphogenesis. Structural proteins are encoded by retroviruses and many RNA viruses as part of large polyproteins. Their proteolytic release is a prerequisite to particle assembly; consequent structural rearrangement of the capsid domains serves to regulate and direct association and assembly of capsid subunits. The second general role of proteolysis is in assembly-dependent maturation of virus particles, which is accompanied by the acquisition of infectivity.

Key words: Virus polyprotein, virus assembly, virus maturation, retrovirus, picornavirus, cysteine proteinase, aspartic proteinase

References

  • 1.Acharya R., Fry E., Stuart D., Fox G., Rowlands D., Brown F. The three-dimensional structure of foot-and-mouth disease virus at 2–9 Å resolution. Nature. 1989;337:709–716. doi: 10.1038/337709a0. [DOI] [PubMed] [Google Scholar]
  • 2.Anderson C. W. The proteinase polypeptide of adenovirus serotype 2 virions. Virology. 1990;177:259–272. doi: 10.1016/0042-6822(90)90479-B. [DOI] [PubMed] [Google Scholar]
  • 3.Anderson C. W., Young M. E., Flint S. J. Characterization of the adenovirus 2 virion protein, μ. Virology. 1989;172:506–612. doi: 10.1016/0042-6822(89)90193-1. [DOI] [PubMed] [Google Scholar]
  • 4.Arnold E., Luo M., Vriend G., Rossmann M. G., Palmenberg A. C., Farks G. D., Nicklin M. J. H., Wimmer E. Implications of the picornavirus capsid structure for polyprotein processing. Proc. natl Acad. Sci. USA. 1987;84:21–25. doi: 10.1073/pnas.84.1.21. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Arnold E., Rossmann M. G. Analysis of the structure of a common cold virus, human rhinorirus 14, refined at a resolution of 3.0 Å. J. molec. biol. 1990;211:763–801. doi: 10.1016/0022-2836(90)90076-X. [DOI] [PubMed] [Google Scholar]
  • 6.Bazan J. F., Fletterick R. J. Viral cysteine proteases are homologous to the trypsin-like family of serine proteases: structural and functional implications. Proc. natl. Acad. Sci. USA. 1988;85:7872–7876. doi: 10.1073/pnas.85.21.7872. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Bieth E., Gabus C., Darlix J.-L. A study of the dimer formation of Rous sarcoma virus RNA and of its effect on viral protein synthesis in vitro. Nucl. Acids Res. 1990;18:119–127. doi: 10.1093/nar/18.1.119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Black L. W., Showe M. K. Morphogenesis of the T4 head. In: Mathews C. K., Kutter E. M., Mosig G., Berget P. B., editors. Bacteriophage T4. Washington, D. C.: American Society of Microbiology; 1983. [Google Scholar]
  • 9.Boege U., Ko D. S. W., Scraba D. G. Toward an in vitro system for picornavirus assembly: purification of mengovirus 14S capsid precursor particles. J. Virol. 1986;57:275–284. doi: 10.1128/jvi.57.1.275-284.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Brault V., Hibrand L., Candresse T., Le Gall O., Dunez J. Nucleotide sequence and genetic organization of Hungarian grapevine chrome mosaic nepovirus RNA2. Nucl. Acids Res. 1989;17:7809–7819. doi: 10.1093/nar/17.19.7809. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.burnette W. N., Holladay L. A., Mitchell W. M. Physical and chemical properties of moloney murine leukemia virus p30 protein: a major core structural component exhibiting high helicity and selfassociation. J. molec. Biol. 1976;107:131–143. doi: 10.1016/s0022-2836(76)80022-8. [DOI] [PubMed] [Google Scholar]
  • 12.Caspar D. L. D., Klug A. Physical principles in the construction of regular viruses, Cold Spring Harbor Symp. Quant. Biol. 1962;27:1–24. doi: 10.1101/sqb.1962.027.001.005. [DOI] [PubMed] [Google Scholar]
  • 13.Cepko C. L., Sharp P. A. Assembly of adenovirus major capsid protein is mediated by a nonvirion protein. Cell. 1982;31:407–415. doi: 10.1016/0092-8674(82)90134-9. [DOI] [PubMed] [Google Scholar]
  • 14.Chatterjee P. K., Flint S. J. Adenovirus type 2 endoproteinase: an unusual phosphoprotein enzyme matured by autocatalysis. Proc. natl Acad. Sci. USA. 1987;84:714–718. doi: 10.1073/pnas.84.3.714. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.Chen Z., Stauffacher C., Li Y., Schmidt T., Bomu W., Kamer G., Shanks M., Lomonossoff G., Johnson J. E. Protein-RNA interactions in an icosahedral virus at 3.0 Å resolution. Science. 1989;245:154–159. doi: 10.1126/science.2749253. [DOI] [PubMed] [Google Scholar]
  • 16.Chen Z., Stauffacher C., Schmidt T., Fisher A., Johnson J. E. RNA packaging in Bean Pod Mottle Virus. In: Brinton M. A., Heinz F. X., editors. New Aspects of Positive-strand Viruses. Washington, D.C.: American Society for Microbiology; 1990. pp. 218–226. [Google Scholar]
  • 16a.Choi H.-K., Tong L., Minor W., Dumas P., Boege U., Rossmann M. G., Wengler G. Structure of Sindbis virus core protein reveals a chymotrypsin-like serine proteinase and the organization of the virion. Nature. 1991;354:37–43. doi: 10.1038/354037a0. [DOI] [PubMed] [Google Scholar]
  • 17.Chow M., Newman J. F. E., Filman D., Hogle J. M., Rowlands D. J., Brown F. Myristoylation of picornavirus capsid protein VP4 and its structural significance. Nature. 1987;327:482–486. doi: 10.1038/327482a0. [DOI] [PubMed] [Google Scholar]
  • 18.Clavel F., Orenstein J. M. A mutant of human immunodeficiency virus with reduced RNA packaging and abnormal particle morphology. J. Virol. 1990;64:5230–5234. doi: 10.1128/jvi.64.10.5230-5234.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19.Compton S. R., Nelsen B., Kirkegaard K. Temperature sensitive poliovirus mutant fails to cleave VP0 and accumulates provirions. J. Virol. 1990;63:4067–4075. doi: 10.1128/jvi.64.9.4067-4075.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20.Crawford S., Goff S. P. A deletion mutation in the 5′ part of thepol gene of moloney murine leukemia virus blocks proteolytic processing of thegag andpol polyproteins. J. Virol. 1985;53:899–907. doi: 10.1128/jvi.53.3.899-907.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21.Crick F. H. C., Watson J. D. Virus structure: general principles. In: Wolstenholme G. E. W., Millar E. C. P., editors. Ciba Foundation Symposium on the Nature of Viruses. London: Churchill; 1957. pp. 5–13. [Google Scholar]
  • 22.Dasgupta R., Sgro S. Nucleotide sequences of three nodavirus RNA 2's: the messengers for their coat protein precursors. Nucl. Acids Res. 1989;17:7525–7526. doi: 10.1093/nar/17.18.7525. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.de Groot R. J., Hardy W. R., Shirako Y., Strauss J. H. Cleavage-site preferences of Sindbis virus polyproteins containing the nonstructural proteinase. Evidence for temporal regulation of polyprotein processing in vivo. EMBO J. 1990;9:2631–2638. doi: 10.1002/j.1460-2075.1990.tb07445.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23a.Dessens J. T., Lomonossoff G. P. Mutational analysis of the putative catalytic triad of the cowpea mosaic virus 24K protease. Virology. 1991;184:738–746. doi: 10.1016/0042-6822(91)90444-G. [DOI] [PubMed] [Google Scholar]
  • 24.D'Halluin J. C., Milleville M., Martin G. R., Boulanger P. Temperature-sensitive mutant of adenovirus type 2 blocked in virion assembly: accumulation of light intermediate particle. J. Virol. 1978;26:344–356. doi: 10.1128/jvi.26.2.344-356.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25.Dickson C., Eisenman R., Fan H., Hunter E., Teich N. Protein biosynthesis and assembly. In: Weiss R., Teich N., Varmus H., Coffin J., editors. RNA Tumor Viruses. New York: Cold Spring Harbor Laboratory Press, Cold Spring Harbor; 1984. pp. 513–548. [Google Scholar]
  • 26.Dorner A. J., Dorner L. F., Larsen G. R., Wimmer E., Anderson C. W. Identification of the initiation site of poliovirus polyprotein synthesis. J. Virol. 1982;42:1017–1028. doi: 10.1128/jvi.42.3.1017-1028.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27.Dougherty W. G., Cary S. M., Parks T. D. Molecular genetic analysis of a plant virus polyprotein cleavage site: a model. Virology. 1989;171:356–364. doi: 10.1016/0042-6822(89)90603-X. [DOI] [PubMed] [Google Scholar]
  • 28.Dougherty W. G., Parks T. D. Molecular genetic and biochemical evidence for the involvement of the heptapeptide cleavage sequence in determining the reaction profile at two tobacco etch virus cleavage sites in cell-free assays. Virology. 1989;172:145–155. doi: 10.1016/0042-6822(89)90116-5. [DOI] [PubMed] [Google Scholar]
  • 29.Felsenstein K. M., Goff S. P. Expression of thegag-pol fusion protein of moloney murine leukemia virus withoutgag protein does not induce virion formation or proteolytic processing. J. Virol. 1988;62:2179–2182. doi: 10.1128/jvi.62.6.2179-2182.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30.Filman D. J., Syed R., Chow M., Macadam A. J., Minor P. D., Hogle J. M. Structural factors that control conformational transitions and serotype specificity in type 3 poliovirus. EMBO J. 1989;8:1567–1579. doi: 10.1002/j.1460-2075.1989.tb03541.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31.Fricks C. E., Hogle J. M. Cell-induced conformational changes in poliovirus: externalization of the amino terminus of VP1 is responsible for liposome binding. J. Virol. 1990;64:1934–1945. doi: 10.1128/jvi.64.5.1934-1945.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 32.Fuller S. D. The T=4 envelope of sindbis virus is organized by interactions with a complementary T=3 capsid. Cell. 1987;48:923–934. doi: 10.1016/0092-8674(87)90701-X. [DOI] [PubMed] [Google Scholar]
  • 33.Fuller S. D., Argos P. Is sindbis a simple picornavirus with an evelope. EMBO J. 1989;6:1099–1105. doi: 10.1002/j.1460-2075.1987.tb04864.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 34.Gallagher T. M., Rueckert R. R. Assembly-dependent maturation cleavage in provirions of a small icosahedral insect ribovirus. J. Virol. 1988;62:3399–3406. doi: 10.1128/jvi.62.9.3399-3406.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 35.Gebhardt A. J., Bosch V., Ziemiecki A., Friis R. R. Rous sarcoma virus p19 and gp35 can be chemically cross-linked to high molecular weight complexes. An insight into viral association. J. molec. Biol. 1984;174:297–317. doi: 10.1016/0022-2836(84)90340-1. [DOI] [PubMed] [Google Scholar]
  • 36.Geelen J. L. M. C., van Kammen A., Verduin B. J. M. Structure of the capsid of cowpea mosaic virus. The chemical subunit: molecular weight and number of subunits per particle. Virology. 1972;49:205–213. doi: 10.1016/s0042-6822(72)80022-9. [DOI] [PubMed] [Google Scholar]
  • 37.Gelderblom H. R., Özel M., Pauli G. morphogenesis and morphology of HIV. Structure-function relations. Archs Virol. 1989;106:1–13. doi: 10.1007/BF01311033. [DOI] [PubMed] [Google Scholar]
  • 38.Gheysen D., Jacobs E., de Foresta F., Thiriart C., Francotte M., Thines D., de Wilde M. Assembly and release of HIV-1 precursor Pr55gag virus-like particles from recombinant baculovirus-infected insect cell. Cell. 1989;59:103–112. doi: 10.1016/0092-8674(89)90873-8. [DOI] [PubMed] [Google Scholar]
  • 39.Goldbach R., van Kammen A. Structure, replication and expression of the bipartite genome of cowpea mosaic virus. In: Davies J. W., editor. Molecular Plant Virology, vol. 2. Boca Raton, FL: CRC Press; 1985. pp. 83–120. [Google Scholar]
  • 40.Goldbach R. Genome similarities between positive-strand RNA viruses from plants and animals. In: Brinton M. A., Heinz F. X., editors. New Aspects of Positive-strand Viruses. Washington, D.C.: American Society for Microbiology; 1990. pp. 3–11. [Google Scholar]
  • 41.Gonda M. A., Wong-Staal F., Gallo R. C., Clements J. E., Narayan O., Gilden R. V. Sequence homology and morphologic similarity of HTLV-III and visna virus, a pathogenic lentivirus. Science. 1985;227:173–177. doi: 10.1126/science.2981428. [DOI] [PubMed] [Google Scholar]
  • 42.Gorbalenya A. E., Svitkin Y. V., Kazachkov Y. A., Agol V. I. Encephalomyocarditis virus-specific polypeptide p22 is involved in the processing of the viral precursor polypeptides. FEBS Letts. 1979;108:1–5. doi: 10.1016/0014-5793(79)81164-3. [DOI] [PubMed] [Google Scholar]
  • 43.Gorbalenya A. E., Donchenko A. P., Blinov V. M., Koonin E. V. Cysteine proteases of positive strand RNA viruses and chymotrypsin-like serine proteases. FEBS Letts. 1989;243:103–114. doi: 10.1016/0014-5793(89)80109-7. [DOI] [PubMed] [Google Scholar]
  • 44.Gorbalenya A. E., koonin E. V., Donchenko A. P., Blinov V. M. Coronavirus genome: prediction of putative functional domains in the non-structural polyprotein by comparative amino acid sequence analysis. Nucl. Acids Res. 1989;17:4847–4861. doi: 10.1093/nar/17.12.4847. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 44a.Gorbalenya A. E., Koonin E. V., Lai M. M.-C. Putative papain-related thiol proteases of positive-strand RNA viruses. Identification of rubi-and aphthovirus proteases and delineation of a novel conserved domain associated with proteases of rubi-, α-and coronaviruses. FEBS Letts. 1991;288:201–205. doi: 10.1016/0014-5793(91)81034-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 45.Göttlinger H. G., Sodroski J. G., Haseltine W. A. Role of capsid precursor processing and myristoylation in morphogenesis and infectivity of human immunodeficiency virus type, 1. Proc. natl Acad. Sci. USA. 1989;86:5781–5785. doi: 10.1073/pnas.86.15.5781. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 46.Guttman N., Baltimore D. Morphogenesis of poliovirus. IV. Existence of particles sedimenting at 150S and having the properties of provirion. J. Virol. 1977;23:363–367. doi: 10.1128/jvi.23.2.363-367.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 47.Hahn C. S., Strauss J. H. Sited-directed mutagenesis of the proposed catalytic amino acids of the sindbis virus capsid protein autoprotease. J. Virol. 1990;64:3069–3073. doi: 10.1128/jvi.64.6.3069-3073.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 47a.Hämmerle T., Hellen C. U. T., Wimmer E. Site-directed mutagenesis of the putative catalytic triad of pollowirus 3C proteinase. J. biol. Chem. 1991;26:5412–5416. [PubMed] [Google Scholar]
  • 48.Hannan C., Raptis L., Dery C., Weber J. Biological and structural studies with an adenovirus type 2 temperature-sensitive mutant defective for uncoating. Intervirology. 1983;19:213–223. doi: 10.1159/000149363. [DOI] [PubMed] [Google Scholar]
  • 49.Harber J. J., Bradley J., Anderson C. W., Wimmer E. The catalysis of the poliovirus VP0 maturation, is not mediated by serine 10 of VP2. J. Virol. 1990;65:326–334. doi: 10.1128/jvi.65.1.326-334.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 50.Harrison, B. D., and Murrant, A. F., Nepovirus group. Descriptions of plant viruses No. 185. Commonwealth Mycological Association/Association of Applied Biology 1977.
  • 51.Harrison S. C. Virus structure: high-resolution perspectives. Adv. Virus Research. 1983;28:175–240. doi: 10.1016/s0065-3527(08)60724-1. [DOI] [PubMed] [Google Scholar]
  • 52.Hellen C. U. T., Kräusslich H. G., Wimmer E. Proteolytic processing of polyproteins in the replication of RNA viruses. Biochemistry. 1989;28:9881–9890. doi: 10.1021/bi00452a001. [DOI] [PubMed] [Google Scholar]
  • 52a.Hellen C. U. T., Fäcke M., Kräusslich H. G., Lee C. K., Wimmer E. Characterization of poliovirus 2A proteinase by mutational analysis: Residues required for autocatalytic activity are essential for induction of cleavage of eukaryotic initiation factor 4F polypeptide p220. J. Virol. 1991;65:4226–4231. doi: 10.1128/jvi.65.8.4226-4231.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 52b.Hellen, C. U. T., and Wimmer, E., Maturation of poliovirus capsid proteins. Virology (1992) in press. [DOI] [PubMed]
  • 53.Hogle J. M., Chow M., Filman D. J. Three-dimensional structure of poliovirus at 2.9 Å resolution. Science. 1985;229:1358–1365. doi: 10.1126/science.2994218. [DOI] [PubMed] [Google Scholar]
  • 54.Hosur M. V., Schmidt T., Tucker R. C., Johnson J. E., Gallagher T. M., Selling B. H., Rueckert R. R. Structure of an insect virus at 3.0 Å resolution. Proteins. 1988;2:167–176. doi: 10.1002/prot.340020302. [DOI] [PubMed] [Google Scholar]
  • 55.Hsiao C. L., Black L. W. DNA packaging and pathway of bacteriophage T4 head assembly. Proc. natl Acad. Sci. USA. 1977;74:3652–3656. doi: 10.1073/pnas.74.9.3652. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 56.Hsu H.-W., Schwartzberg P., Goff S. P. Point mutations in the p30 domain of thegag gene of moloney murine keukemia virus. Virology. 1985;142:211–214. doi: 10.1016/0042-6822(85)90435-0. [DOI] [PubMed] [Google Scholar]
  • 57.Jackson R. J. An unusual coordinated cleavage event in the processing of encephalomyocarditis virus polypeptides. Virology. 1986;172:363–366. doi: 10.1016/0042-6822(89)90141-4. [DOI] [PubMed] [Google Scholar]
  • 58.Jore J., de Geus B., Jackson R. J., Pouwels P. H., Enger-Valk B. E. Poliovirus protein 3CD is the active protease for processing of the precursor protein P1 in vitro. J. gen. Virol. 1988;69:1627–1636. doi: 10.1099/0022-1317-69-7-1627. [DOI] [PubMed] [Google Scholar]
  • 59.Kaesberg P., Dasgupta R., Sgro J.-Y., Wery J.-P., Selling B. H., Hosur M. V., Johnson J. E. Structural homology among four nodaviruses as deduced by sequencing and X-ray crystallography. J. molec. Biol. 1990;214:423. doi: 10.1016/0022-2836(90)90191-N. [DOI] [PubMed] [Google Scholar]
  • 60.Kay J., Dunn B. M. Viral proteinases: weakness in strength. Biochim. biophys. Acta. 1990;1048:1–18. doi: 10.1016/0167-4781(90)90015-t. [DOI] [PubMed] [Google Scholar]
  • 60a.Kean K. M., Teterina N. L., Marc D., Girard M. Analysis of putative active site residues of poliovirus 3C protease. Virology. 1991;181:609–619. doi: 10.1016/0042-6822(91)90894-H. [DOI] [PubMed] [Google Scholar]
  • 61.Kellenberger E. Studies on the morphopoiesis of the head of phage T-even. V. The components of the T4 capsid and other, capsid-related structures. Virology. 1968;24:549–561. doi: 10.1016/0042-6822(68)90074-3. [DOI] [PubMed] [Google Scholar]
  • 62.Kim S., Smith T. J., Chapman M. S., Rossmann M. G., Pevear D. C., Dutko F. J., Felock P. J., Diana G. D., McKinlay M. A. Crystal structure of human rhinovirus serotype 1A (HRV1A) J. molec. Biol. 1989;210:91–111. doi: 10.1016/0022-2836(89)90293-3. [DOI] [PubMed] [Google Scholar]
  • 63.Kistler J., Aebi U., Onorato L., ten Heggeler B., Showe M. K. Structural changes during transformation of bacteriophage T4 polyheads: characterization of the initial and final states by freeze-drying and shadowing. Fab-fragment-labelled preparations. J. molec. Biol. 1978;126:571–589. doi: 10.1016/0022-2836(78)90059-1. [DOI] [PubMed] [Google Scholar]
  • 64.Kitamura N., Semler B. L., Rothberg P. G., Larsen G. R., Adler C. J., Dorner A. J., Emini E. A., Hanecak R., Lee J., van der Werf S., Anderson C. W., Wimmer E. Primary structure, gene organization and polypeptide expression of poliovirus RNA. Nature. 1981;291:547–553. doi: 10.1038/291547a0. [DOI] [PubMed] [Google Scholar]
  • 65.Kohl N. E., Emini E. A., Schleif W. A., Davis L. J., Heimbach J. C., Dixon R. A. F., Scolnick E. M., Sigal I. S. Active human immunodeficiency virus protease is required for viral infectivity. Proc. natl Acad. Sci. USA. 1988;85:4686–4690. doi: 10.1073/pnas.85.13.4686. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 66.Korb J., Travnicek M., Riman J. The oncornavirus maturation process: quantitative correlation between morphological changes and conversion of genomic virion RNA. Intervirology. 1976;7:211–224. doi: 10.1159/000149954. [DOI] [PubMed] [Google Scholar]
  • 67.Kräusslich H.-G., Wimmer E. Viral proteinases. A. Rev. Biochem. 1988;57:701–754. doi: 10.1146/annurev.bi.57.070188.003413. [DOI] [PubMed] [Google Scholar]
  • 68.Kräusslich H.-G., Oroszlan S., Wimmer E., editors. Viral Proteinases as Targets for Chemotherapy. Cold Spring Harbor, New York: Cold Spring Harbor Laboratory Press; 1989. [Google Scholar]
  • 69.Kräusslich H.-G., Hölscher C., Reuer Q., Harber J., Wimmer E. Myristoylation of the poliovirus polyprotein is required for proteolytic processing of the capsid and for viral infectivity. J. Virol. 1990;64:2433–2436. doi: 10.1128/jvi.64.5.2433-2436.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 70.Krishnaswamy S., Rossmann M. G. Structural refinement and analysis of Mengo virus. J. molec. Biol. 1990;211:803–844. doi: 10.1016/0022-2836(90)90077-Y. [DOI] [PubMed] [Google Scholar]
  • 71.Larsen G. W., Anderson C. W., Dorner A. J., Semler B. L., Wimmer E. Cleavage sites within the poliovirus capsid protein precursors. J. Virol. 1982;41:340–344. doi: 10.1128/jvi.41.1.340-344.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 72.Lawson M. A., Semler B. L. Picornavirus protein processing: enzymes, substrates and genetic regulation. Curr. Top. Microbiol. Immun. 1990;161:49–87. [PubMed] [Google Scholar]
  • 73.Le Grice S. F. J., Mills J., Mous J. Active site mutagenesis of the AIDS virus protease and its alleviation bytrans complementation. EMBO J. 1988;7:2547–2553. doi: 10.1002/j.1460-2075.1988.tb03103.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 73a.Lomonossoff G. P., Johnson J. E. The synthesis and structure of comovirus capsids. Prog. Biophys. molec. Biol. 1991;55:107–137. doi: 10.1016/0079-6107(91)90003-B. [DOI] [PubMed] [Google Scholar]
  • 74.Lopez-Ortin C., Simon-Mateo C., Martinez L., Vinuela E. Gly-Gly-X, a novel consensus sequence for the proteolytic processing of viral and cellular proteins. J. biol. Chem. 1989;264:9107–9110. [PubMed] [Google Scholar]
  • 75.Luo M., Vriend G., Kamer G., Minor I., Arnold E., Rossman M. G., Boege U., Scraba D. G., Duke G. M., Palmenberg A. C. The atomic resolution of Mengo virus at 3.0. Å resolution. Science. 1987;235:182–191. doi: 10.1126/science.3026048. [DOI] [PubMed] [Google Scholar]
  • 76.McDonald J. G., Bancroft J. B. Assembly studies on potato virus Y and its coat protein. J. gen. Virol. 1977;35:251–263. [Google Scholar]
  • 77.Marc D., Drugeon G., Haenni A.-L., Girard M., van der Werf S. Role of myristoylation of poliovirus capsid protein VP4 as determined by site-directed mutagenesis of its N-terminal sequence. EMBO J. 1989;8:2661–2668. doi: 10.1002/j.1460-2075.1989.tb08406.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 78.Mayo M. A., Murant A. F., harrison B. D. New evidence on the structure of nepoviruses. J. gen. Virol. 1971;12:175–178. doi: 10.1099/0022-1317-12-2-175. [DOI] [PubMed] [Google Scholar]
  • 79.Meek T. D., Dayton B. D., Metcalf B. W., Dreyer G. B., Strickler J. E., Gorniak J. G., Rosenberg M., Moore M. L., Magaard V. W., DeBouck C. Human immunodeficiency virus 1 protease expressed inEscherichia coli behaves as a dimeric aspartic protease. Proc. natl Acad. Sci. USA. 1989;86:1841–1845. doi: 10.1073/pnas.86.6.1841. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 80.Mervis R. J., Ahmad N., Lillehoj E. P., Raum M. G., Salazar F. H. R., Chan H. W., Venkatesan S. Thegag gene products of human immunodeficiency virus type 1: alignment within thegag open reading frame, identification of posttranslational modifications, and evidence for alternativegag precursors. J. Virol. 1988;62:3993–4002. doi: 10.1128/jvi.62.11.3993-4002.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 81.Miller M., Jaskolski M., Rao J. K. M., Leis J., Wlodawer A. Crystal structure of a retroviral protease proves relationship to aspartic protease family. Nature. 1989;337:576–579. doi: 10.1038/337576a0. [DOI] [PubMed] [Google Scholar]
  • 82.Nicklin M. J. H., Toyoda H., Murray M. G., Wimmer E. Proteolytic processing in the replication of polio and related viruses. Bio/Technology. 1989;4:33–42. doi: 10.1038/nbt0186-33. [DOI] [Google Scholar]
  • 83.Nicklin M. J. H., Kräusslich H.-G., Toyoda H., Dunn J. J., Wimmer E. Poliovirus polypeptide precursors: expression in vitro and processing by exogenous 3C and 2A proteinase. Proc. natl Acad. Sci. USA. 1987;84:4002–4006. doi: 10.1073/pnas.84.12.4002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 84.Nicklin M. J. H., Harris K. S., Pallai P. V., Wimmer E. Poliovirus protenase 3C: large-scale expression, purification, and specific cleavage activity on natural and synthetic substrates in vitro. J. Virol. 1988;62:4586–4593. doi: 10.1128/jvi.62.12.4586-4593.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 84a.Oh C.-S., Carrington J. C. Identification of essential residues in potyvirus proteinase HC-Pro by site-directed mutagenesis. Virology. 1989;173:692–699. doi: 10.1016/0042-6822(89)90582-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 85.Onorato L., Stirner B., Showe M. K. Isolation and characterization of bacteriophage T4 mutant preheads. J. Virol. 1978;27:409–426. doi: 10.1128/jvi.27.2.409-426.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 86.Pallai P. V., Burkhardt F., Skoog M., Schreiner K., Bax P., Cohen K. A., Hansen G., Palladino D. E. H., Harris K. S., Nicklin M. J., Wimmer E. Cleavage of synthetic peptides by purified poliovirus 3C proteinase. J. biol. Chem. 1989;264:9738–9741. [PubMed] [Google Scholar]
  • 87.Palmenberg A. C. In vitro synthesis and assembly of picornaviral capsid intermediate structures. J. Virol. 1982;44:900–906. doi: 10.1128/jvi.44.3.900-906.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 88.Palmenberg A. C. Proteolytic processing of picornaviral polyprotein. A. Rev. Microb. 1990;44:603–623. doi: 10.1146/annurev.mi.44.100190.003131. [DOI] [PubMed] [Google Scholar]
  • 89.Parks G. D., Duke G. M., Palmenberg A. C. Encephalomyocarditis virus 3C protease: efficient cell-free expression from clones which link virall 5′ noncoding sequences to the P3 region. J Virol. 1986;60:376–384. doi: 10.1128/jvi.60.2.376-384.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 90.Parks G. D., Palmenberg A. C. Site-specific, mutations at a picornavirus VP3/VP1 cleavage site disrupt in vitro processing and assembly of capsid precursors. J. Virol. 1987;61:3680–4687. doi: 10.1128/jvi.61.12.3680-3687.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 91.Partin K., Kräusslich H.-G., Ehrlich L., Wimmer E., Carter C. Mutational analysis of a native substrate of the human immunodeficiency virus type 1 proteinase. J. Virol. 1990;64:3938–3947. doi: 10.1128/jvi.64.8.3938-3947.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 92.Paul A. V., Schultz A., Pincus S. E., Oroszlan S., Wimmer E. Capsid protein VP4 of poliovirus is N-myristoylated. Proc. natl Acad Sci. USA. 1987;84:7827–7831. doi: 10.1073/pnas.84.22.7827. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 93.Pearl L. H., Taylor W. R. A structural model for the retroviral proteases. Nature. 1987;329:351–354. doi: 10.1038/329351a0. [DOI] [PubMed] [Google Scholar]
  • 94.Pelham H. R. B. Translation of encephalomyocarditis virus RNA in vitro yields an active proteolytic processing enzyme. Eur. J. Biochem. 1978;85:457–462. doi: 10.1111/j.1432-1033.1978.tb12260.x. [DOI] [PubMed] [Google Scholar]
  • 95.Phillips B. A., Wiemert S. In vitro assembly of poliovirus. V. Evidence that the self-assembly activity of 14S particles is independent of extract assembly factor(s) and host proteins. Virology. 1978;88:92–104. doi: 10.1016/0042-6822(78)90113-7. [DOI] [PubMed] [Google Scholar]
  • 96.Prats A.-C., Roy C., Wang P., Erard M., Housset V., Gabus C., Paoletti C., Darlix J.-L. Cis elements andtrans-acting factors involved in dimer formation of murine leukemia virus RNA. J. Virol. 1990;64:774–783. doi: 10.1128/jvi.64.2.774-783.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 97.Putnak J. R., Phillips B. A. Picornaviral structure and assembly. Microb. Rev. 1981;45:287–315. doi: 10.1128/mr.45.2.287-315.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 98.Rao V. B., Black L. W. Evidence that a phage T4 DNA packaging enzyme is a processed form of the major capsid gene product. Cell. 1986;42:967–977. doi: 10.1016/0092-8674(85)90293-4. [DOI] [PubMed] [Google Scholar]
  • 99.Reanney D. The molecular evolution of viruses. In: Mahy B. W. J., Pattison J. R., editors. The Microbe 1984. Part 1. Viruses. Cambridge: Society for General Microbiology/Cambridge University Press; 1984. pp. 176–196. [Google Scholar]
  • 100.Rhee S. S., Hunter E. Myristoylation is required for intracellular transport but not for assembly of D-type retrovirus capsids. J. Virol. 1987;61:1045–1053. doi: 10.1128/jvi.61.4.1045-1053.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 101.Rhee S. S., Hunter E. Structural role of the matrix protein of type D retroviruses ingag polyprotein stability and capsid assembly. J. Virol. 1990;64:4383–3289. doi: 10.1128/jvi.64.9.4383-4389.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 102.Rice C. M., Strauss E. G., Strauss J. H. Structure of the flavivirus genome. In: Schlesinger S., Schlesinger M., editors. The Togaviruses and Flaviviruses. New York: Plenum; 1986. pp. 279–327. [Google Scholar]
  • 103.Robertson B. H., Grubman M. J., Weddell G. N., Moore D. M., Welsh J. D., Fischer T., Dowbenko D. J., Yansura D. G., Small B., Kleid D. G. Nucleotide and amino acid sequence coding for polypeptides of foot-and-mouth disease virus type A12. J. Virol. 1985;54:651–660. doi: 10.1128/jvi.54.3.651-660.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 104.Rossmann M. G., Arnold E., Erickson J. W., Frankenberger E. A., Griffith J. P., Hecht H.-J., Johnson J. E., Kamer G., Luo M., Mosser A. G., Rueckert R. R., Sherry B., Vriend G. Structure of a human common cold virus and functional relationship to other picornaviruses. Nature. 1985;317:145–153. doi: 10.1038/317145a0. [DOI] [PubMed] [Google Scholar]
  • 105.Rossmann M. G. Antiviral agents targeted to interact with viral capsid proteins and a possible application to human immunodeficiency virus. Proc. natl Acad. Sci. USA. 1988;85:4625–4627. doi: 10.1073/pnas.85.13.4625. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 106.Rossmann M. G., Johnson J. E. Icosahedral RNA virus structure. A. Rev. Biochem. 1989;58:533–573. doi: 10.1146/annurev.bi.58.070189.002533. [DOI] [PubMed] [Google Scholar]
  • 107.Rueckert R. R. Picornaviridae and their replication. In: Fields B. N., Knipe D. M., Chanock R. M., Hirsch M. S., Melnick J. L., Morath T. P., Roizman B., editors. Virology. New York: Raven Press; 1990. pp. 507–548. [Google Scholar]
  • 108.Rueckert R. R., Wimmer E. Systematic nomenclature of picornavirus proteins. J. Virol. 1984;50:957–959. doi: 10.1128/jvi.50.3.957-959.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 108a.Ryan M. D., King A. M. Q., Thomas G. O. Cleavage of foot-and-mouth disease virus polyprotein is mediated by residues within a 19 amino acid sequence. J. gen. Virol. 1991;72:2727–2732. doi: 10.1099/0022-1317-72-11-2727. [DOI] [PubMed] [Google Scholar]
  • 108b.Schapira R., Nuss D. L. Gene expresson by a hypovirullence-assocaited virus of the chestnut blight fungus involves two papainlike protease activities. J. biol. Chem. 1991;266:19419–19425. [PubMed] [Google Scholar]
  • 109.Schultz A. M., Henderson L. E., Oroszlan S. Fatty acylation of proteins. A. Rev. cell. Biol. 1988;4:611–647. doi: 10.1146/annurev.cb.04.110188.003143. [DOI] [PubMed] [Google Scholar]
  • 110.Schultz A. M., Rein A. Unmyristylated moloney murine leukaemia virus Pr65gag is excluded from virus assembly and maturation events. J. Virol. 1989;63:2370–2373. doi: 10.1128/jvi.63.5.2370-2373.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 111.Shih C. T., Shih D. S. Cleavage of the capsid protein precursors of encephalomyocarditis virus in rabbit reticulocyte lysates. J. Virol. 1981;40:942–945. doi: 10.1128/jvi.40.3.942-945.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 112.Shih D. S., Shih C. T., Zimmern D., Rueckert R. R., Kaesberg P. Translation of encephalomyocarditis virus RNA in reticulocyte lysates: kinetic analysis of the formation of virion proteins and a protein required for processing. J. Virol. 1979;30:472–480. doi: 10.1128/jvi.30.2.472-480.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 113.Showe M. K., Isobe E., Onorato L. Bacteriophage T4 prehead proteinase. I. Purification and properties of a bacteriophage enzyme which cleaves the capsid precursor proteins. J. molec. Biol. 1976;107:35–54. doi: 10.1016/s0022-2836(76)80016-2. [DOI] [PubMed] [Google Scholar]
  • 114.Showe M. K., Isobe E., Onorato L. Bacteriophage T4 prehead proteinase. II. Its cleavage from the product of gene 21 and regulation in phage-infected cells. J. molec. Biol. 1976;107:55–69. doi: 10.1016/s0022-2836(76)80017-4. [DOI] [PubMed] [Google Scholar]
  • 115.Sorger P. K., Stockley P. G., Harrison S. C. Structure and assembly of turnip crinkle virus. II. Mechanism of reassembly in vitro. J. molec. Biol. 1986;191:639–658. doi: 10.1016/0022-2836(86)90451-1. [DOI] [PubMed] [Google Scholar]
  • 116.Spence R. P., Walker J., Jarvill W. M., Ferns R. B., Tedder R. S., Sattentau Q., Weber J., Parry N. R., Highfield P. E. The expression inEscherichia coli of sequences coding for the p18 protein of human immunodeficiency virus and the use of the recombinant protein in characterizing a panel of monoclonal antibodies against the viral p18 protein. J. gen. Virol. 1979;70:2853–2863. doi: 10.1099/0022-1317-70-11-2853. [DOI] [PubMed] [Google Scholar]
  • 117.Stauffacher C. V., Usha R., Harrington M., Schmidt T., Hosur M. V., Johnson J. E. The structure of cowpea mosaic virus at 3.5 Å resolution. In: Moras D., Strandberg B., Suck D., Wilson K., editors. Crystallography in Molecular Biology. New York: Plenum; 1987. pp. 293–308. [Google Scholar]
  • 118.Stewart L., Schatz G., Vogt V. M. Properties of avian retrovirus particles defective in viral protease. J. Virol. 1990;64:5076–5092. doi: 10.1128/jvi.64.10.5076-5092.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 119.Strebel K., Beck E. A second protease of foot-and-mouth disease virus. J. Virol. 1986;58:893–899. doi: 10.1128/jvi.58.3.893-899.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 120.Strong R. K., Harrison S. C. Proteolytic dissection of Sindbis virus core protein. J. Virol. 1990;64:3992–3994. doi: 10.1128/jvi.64.8.3992-3994.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 121.Teich N. Taxonomy of retroviruses. In: Weiss R., Teich N., Varmus H., Coffin J., editors. RNA Tumor Viruses. Cold Spring Harbor, New York: Cold Spring Harbor Laboratory Press; 1984. pp. 25–207. [Google Scholar]
  • 122.Toh H., Ono M., Saigo K., Miyata T. Retroviral proteaselike sequence in the yeast transposon Ty 1. Nature. 1976;315:691. doi: 10.1038/315691a0. [DOI] [Google Scholar]
  • 123.Toyoda H., Nicklin M. J. H., Murray M. G., Anderson C. W., Dunn J. J., Studier F. W., Wimmer E. A second virus-encoded proteinase involved in proteolytic processing of poliovirus polyprotein. Cell. 1986;45:761–770. doi: 10.1016/0092-8674(86)90790-7. [DOI] [PubMed] [Google Scholar]
  • 123a.Valegard K., Liljas L., Fridborg K., Unge T. The three-dimensional structure of bacterial virus MS2. Nature. 1990;345:36–41. doi: 10.1038/345036a0. [DOI] [PubMed] [Google Scholar]
  • 124.Vos P., Verver J., Jaegle M., Wellink J., van Kammern A., Goldbach R. Two viral proteins involved in the proteolytic processing of the cowpea mosai virus polyproteins. Nucl. Acids Res. 1988;16:1967–1985. doi: 10.1093/nar/16.5.1967. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 125.Weaver T. A., Talbot K. J., Panganiban A. T. Spleen necrosis virusgag polyprotein is necessary for particle assembly and release but not for proteolytic processing. J. Virol. 1990;64:2642–2652. doi: 10.1128/jvi.64.6.2642-2652.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 126.Webster A., Russell S., Talbot P., Russell W. C., Kemp G. D. Characterization of the adenovirus proteinase: substrate specificity. J. gen. Virol. 1989;70:3225–3234. doi: 10.1099/0022-1317-70-12-3225. [DOI] [PubMed] [Google Scholar]
  • 127.Wengler G., Boege U., Wengler G., Bischoff H., Wahn K. The core protein of the alphavirus sindbis virus assembles into corelike nucleoproteins with the viral genome RNA and with other single-stranded nucleic acids in vitro. J. Virol. 1982;118:401–410. doi: 10.1016/0042-6822(82)90359-2. [DOI] [PubMed] [Google Scholar]
  • 128.Witte O. N., Baltimore D. Relationship of retrovirus polyprotein cleavages to virion maturation studied with temperature-sensitive murine leukemia virus mutants. J. Virol. 1978;26:750–761. doi: 10.1128/jvi.26.3.750-761.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 129.Wlodawer A., Miller M., Jaskolski M., Sathyanarayana B. K., Baldwin E., Weber I. T., Selk L. M., Clawson L., Scheider J., Kent S. B. H. Conserved folding in retroviral protease: crystal structure of a synthetic HIV-1 protease. Science. 1989;245:616–621. doi: 10.1126/science.2548279. [DOI] [PubMed] [Google Scholar]
  • 130.Yoshinaka Y., Luftig R. B. Murine leukemia virus morphogenesis: cleavage of P70 in vitro can be accompanied by a shift from a concentrically coiled internal strand (‘immature’) to a collapsed (‘mature’) form of the virus core. Proc. natl Acad Sci. USA. 1977;74:3446–3450. doi: 10.1073/pnas.74.8.3446. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 131.Ypma-Wong M.-F., Semler B. L. In vitro molecular genetics as a tool for determining the differential cleavage specificities of the poliovirus 3C proteinase. Nucl. Acids Res. 1987;15:2069–2088. doi: 10.1093/nar/15.5.2069. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 132.Ypma-Wong M.-F., Dewalt P. G., Johnson V. H., Lamb J. G., Semler B. L. Protein 3CD is the major proteinase responsible for cleavage of the P1 capsid precursor. Virology. 1988;166:265–270. doi: 10.1016/0042-6822(88)90172-9. [DOI] [PubMed] [Google Scholar]
  • 133.Ypma-Wong M. F., Filman D. J., Hogle J. M., Semler B. L. Structural domains of the poliovirus polyprotein are major determinants for proteolytic cleavage at Gln-Gly pairs. J. biol. Chem. 1988;263:17846–17856. [PubMed] [Google Scholar]
  • 133a.Yu S. F., Lloyd R. E. Identification of essential amino acids in the functional activity of pollovirus 2A protease. Virology. 1991;182:615–625. doi: 10.1016/0042-6822(91)90602-8. [DOI] [PubMed] [Google Scholar]
  • 134.Zimmern D. Evolution of RNA viruses. In: Holland J. J., Domingo E., Ahlquist P., editors. RNA Genetics. Boca Raton, FL: CRC Press, Inc.; 1988. pp. 211–240. [Google Scholar]

Articles from Experientia are provided here courtesy of Nature Publishing Group

RESOURCES