Summary
The WIN drugs and similar hydrophobic compounds that insert into the capsid of picornaviruses have been shown to block viral uncoating. In some of the human rhinoviruses they also block attachment of virus to cells. Spontaneously occurring drug-resistant mutants of human rhinovirus 14 and poliovirus type 3 were selected for their ability to make plaques in the presence of the selecting drug. The HRV-14 mutants either prevented drug binding or allowed the virus to attach to cells in the presence of drug. About two thirds of the poliovirus mutants were dependent on the presence of drug for plaque formation. In single cycle growth curves, drug was not required for the formation of drug-dependent progeny virus. However, progeny virus grown without drug never accumulated outside of cells, thus making the formation of plaques impossible. This behavior was apparently caused by the extreme thermolability of these mutants. In the absence of drug, heating to 37°C rapidly converted them to non-infectious particles with a sedimentation coefficient of 135S.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Hogle J, Chow M, Filman DJ (1985) Three-dimensional structure of poliovirus at 2.9 A resolution. Science 229: 1358–1365
Rossmann MG, Arnold E, Erickson JW, Frankenberger EA, Griffith JP, Hecht H-J, Johnson JE, Kamer G, Luo M, Mosser AG, Rueckert RR, Sherry B, Vriend G (1985) Structure of a human common cold virus and functional relationship to other picornaviruses. Nature 317: 145–153
Olson NH, Kolatkar PR, Oliveira MA, Cheng RH, Greve JM, McClelland A, Baker TS, Rossmann MG (1993) Structure of a human rhinovirus complexed with its receptor molecule. Proc Natl Acad Sci USA 90: 507–511
Greve JM, Davis G, Meyer AM, Forte CP, Yost SC, Marlor CW, Kamarck ME, McClelland A (1989) The major human rhinovirus receptor is ICAM-1. Cell 56: 839–847
Staunton DE, Merluzzi VJ, Rothlein R, Barton R, Marlin SD, Springer TA (1989) A cell adhesion molecule, IACM-1, is the major surface receptor for rhinoviruses. Cell 56: 849–853
Filman DJ, Syed R, Chow M, Macadam AJ, Minor PD, Hogle JM (1989) Structural factors that control conformational transitions and serotype specificity in type 3 poliovirus. EMBO J 8: 1567–1579
Kim S, Smith TJ, Chapman MS, Rossmann MG, Pevear DC, Dutko FJ, Felock PJ, Diana GD, McKinlay MA (1989) Crystal structure of human rhinovirus serotype 1A (HRV1A). J Mol Biol 210: 91–111
Smith TJ, Kremer MJ, Luo M, Vriend G, Arnold E, Kamer G, Rossmann MG, McKinlay MA, Diana GD, Otto MJ (1986) The site of attachment in human rhinovirus 14 for antiviral agents that inhibit uncoating. Science 233: 1286–1293
Badger J, Minor I, Oliveira MJ, Smith TJ, Griffith JP, Guerin DMA, Krishnaswamy S, Luo M, Rossmann MG, McKinlay MA, Diana GD, Dutko FJ, Fancher M, Rueckert RR, Heinz BA (1988) Structural analysis of a series of antiviral agents complexed with human rhinovirus 14. Proc Natl Acad Sci USA 85: 3304–3308
McKinlay M (1985) WIN 51711, a new systematically active broad-spectrum antipicornavirus agent. J Antimicrob Chemother 16: 284–286
Otto MJ, Fox MP, Fancher MJ, Kuhrt MF, Diana GD, McKinlay MA (1985) In vitro activity of WIN 51711: a new broad-spectrum antipicornavirus drug. Antimicrob Agents Chemother 27: 883–886
Caliguiri LA, McSharry JJ, Lawrence GW (1980) Effect of arildone on modifications of poliovirus in vitro. Virology 105: 86–93
Fox MP, Otto MJ, McKinlay MA (1986) The prevention of rhinovirus and poliovirus uncoating by WIN 51711: a new antiviral drug. Antimicrob Agents Chemother 30: 110–116
Gruenberger M, Pevear D, Diana GD, Kuechler E, Blaas D (1991) Stabilization of human rhinovirus serotpye 2 against pH induced conformational change by antiviral compounds. J Gen Virol 72: 431–433
McSharry JJ, Caliguiri LA, Eggers HJ (1979) Inhibition of uncoating of poliovirus by arildone, a new antiviral drug. Virology 97: 307–315
Zeichhardt H, Otto MJ, McKinlay MA, Willingmann P, Habermehl K-O (1987) Inhibition of poliovirus uncoating by disoxaril (WIN 51711). Virology 160: 281–285
Heinz BA, Rueckert RR, Shepard DA, Dutko FJ, McKinlay MA, Fancher M, Rossmann MG, Badger J, Smith T (1989) Genetic and molecular analysis of spontaneous mutants of human rhinovirus 14 that are resistant to an antiviral compound. J Virol 63: 2476–2485
Pevear DC, Fancher MJ, Felock PJ, Rossmann MG, Miller MS, Diana G, Treasurywala AM, McKinlay MA, Dutko FJ (1989) Conformational change in the floor of the human rhinovirus canyon blocks adsorption to HeLa cell receptors. J Virol 63: 2002–2007
Heinz BA, Shepard DA, Rueckert RR (1990) Escape mutant analysis of a drug-binding site can be used to map functions in the rhinovirus capsid. In: Laver G, Air G (eds) Use of X-ray crystallography in the design of antiviral agents. Academic Press, New York, pp 173–186
Shepard DA, Heinz BA, Rueckert RR (1993) WIN 52035-2 inhibits both attachment and eclipse of human rhinovirus 14. J Virol 67: 2245–2254
Mosser AG, Rueckert RR (1993) WIN 51711-dependent mutants of type 3 poliovirus: evidence that virions decay after release from cells unless drug is present. J Virol 67: 1246–1254
DeSena J, Mandell B (1977) Studies on the in vitro uncoating of poliovirus. II. Characterization of the membrane-modified particle. Virology 78: 554–566
Fricks CE, Hogle JM (1990) Cell-induced conformational changes of poliovirus: externalization of the amino terminus of VP1 is responsible for liposome binding. J Virol 64: 1934–1945
Kaplan G, Freistadt MS, Racaniello VR (1990) Neutralization of poliovirus by cell receptors expressed in insect cells. J Virol 64: 4697–4702
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1994 Springer-Verlag
About this paper
Cite this paper
Mosser, A.G., Shepard, D.A., Rueckert, R.R. (1994). Use of drug-resistance mutants to identify functional regions in picornavirus capsid proteins. In: Brinton, M.A., Calisher, C.H., Rueckert, R. (eds) Positive-Strand RNA Viruses. Archives of Virology Supplementum, vol 9. Springer, Vienna. https://doi.org/10.1007/978-3-7091-9326-6_12
Download citation
DOI: https://doi.org/10.1007/978-3-7091-9326-6_12
Publisher Name: Springer, Vienna
Print ISBN: 978-3-211-82522-8
Online ISBN: 978-3-7091-9326-6
eBook Packages: Springer Book Archive