Multiple Stages of Virus-Receptor Interactions as Shown by Simian Virus 40

  • Leonard C. Norkin
  • Howard A. Anderson
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 408)


None of the many antibiotics that are clinically effective in the fight against bacteria are active against viruses. Furthermore, the search for clinically effective antiviral agents has thus far produced relatively few useful drugs. Nevertheless, adhesion based therapies may be particularly promising in the fight against viruses. First, whereas adhesion may enhance the infectivity of certain bacteria, the interaction of a virus with its receptor is absolutely critical for infection. Furthermore, since virus-receptor interactions are highly specific, a virus can not easily mutate its receptor binding site and remain viable. Thus, the anti-adhesion approach to antivirals is not likely to lead to drug resistant variants. Also, whereas viruses were once thought to interact with a single cell membrane component, an increasing number of viruses are appearing to interact sequentially with multiple distinct cell surface components (Haywood, 1994; Norkin, 1995). Initial binding may be followed by secondary interactions that strengthen adhesion, promote entry, or both. This complexity may be a cause for optimism since it produces additional opportunities for the rational development of drugs that might target initial binding, adhesion strengthening, or entry.


Major Histocompatibility Complex Molecule Simian Virus Early Response Gene Entry Pathway Cytosol Acidification 
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  1. Anderson, H.A., 1995. Ph.D. Thesis, University of Massachusetts, Amherst, MA.Google Scholar
  2. Atwood, W.J., and Norkin, L.C., 1989. Class I major histocompatibility proteins as cell surface receptors for simian virus 40. J. Virol 63:4474–4478.PubMedGoogle Scholar
  3. Breau, W.C., Atwood, W.J., and Norkin, L.C., 1992. Class I major histocompatibility proteins are an essential component of the simian virus 40 receptor. J. Virol. 66:2037–2045.PubMedGoogle Scholar
  4. Breau, W.C., and Norkin, L.C., 1994. Extracellular SV40 activates primary response genes. J. Cell Biochem. Suppl. 18B:254.Google Scholar
  5. Clayson, E.T., and Compans, R.W., 1988. Entry of simian virus 40 is restricted to apical surfaces of polarized epithelial cells. Mol. Cell. Biol. 8:3391–3396.PubMedGoogle Scholar
  6. Clayson, E.T., and Compans, R.W., 1989. Characterization of simian virus 40 receptor moieties on the surface of vero CI008 cells. J. Virol. 63:1095–1100.PubMedGoogle Scholar
  7. Demaria, S., Schwab, R., Gottesman, S.R.S., and Bushkin, Y., 1994. Solubule β2-microglobulin-free class I heavy chains are released from the surface of activated and leukemia cells by a metalloprotease. J. Biol. Chem. 269:6689–6694.PubMedGoogle Scholar
  8. Geleziunas, R., Bour, S., and Wainberg, M.A., 1994. Human immunodeficiency virus type I-associated CD4 downmodulation. Adv. Virus Res. 44:203–266.PubMedCrossRefGoogle Scholar
  9. Golding, H., Dimitrov, D.S., Manischewitz, J., Broder, C.C., Robinson, J., Fabian, S., Littman, D.R., and Lapham, C.K., 1995. Phorbol ester-induced down modulation of tailles CD4 receptors requires prior binding of gpl20 and suggests a role for accessory molecules. J. Virol. 69:6140–6148.PubMedGoogle Scholar
  10. Haywood, A.M., 1994. Virus receptors: binding, adhesion strengthening, and c lenius, A., 1989. Endocytosis of simian virus 40 into the endoplasmic reticulum. J. Cell Biol. 109:2721–2729.Google Scholar
  11. MacKay, R., and Consigli, R.A., 1976. Early events in polyoma virus infection: attachment, penetration and nuclear entry. J. Virol. 19:620–636.PubMedGoogle Scholar
  12. Marsh, M., and Helenius, A., 1989. Virus entry into animal cells. Adv. Virus Res. 36:107–151.PubMedCrossRefGoogle Scholar
  13. Maul, G.G., Rovera, G., Vorbrodt, A., and Abramczuk, J., 1978. Membrane fusion as a mechanism of simian virus 40 entry into different cellular compartments. J. Virol. 28:936–944.PubMedGoogle Scholar
  14. Milici, A.J., Waltrous, N.W., Stukenbrok, H., and Palade, G.E., 1987. Transcytosis of albumin in capillary epithelium. J. Cell Biol. 105:2603–2612.PubMedCrossRefGoogle Scholar
  15. Montesano, R., Roth, J., Robert, A., and Orci, L., 1982. Non-coated membrane invaginations are involved in binding and internalization of tetanus toxins. Nature 296:651–653.PubMedCrossRefGoogle Scholar
  16. Neefjes, J.J., Smit, L., Gehrmann, M., and Ploegh, H.L., 1992. The fate of the three subunits of major histocompatibility class I molecules. Eur. J. Immunol. 22:1609–1614.PubMedCrossRefGoogle Scholar
  17. Norkin, L.C., 1995. Virus receptors: implications for pathogenesis and the design of antiviral agents. Clin. Microbiol. Rev. 8:293–315.PubMedGoogle Scholar
  18. Rothberg, K.G., Heuser, J.E., Danzell, W.C., Ying, Y.-S., Glenney, J.R., and Anderson, R.G.W., 1992. Caveolin, a protein component of caveolae membrane coats. Cell 68:673–682.PubMedCrossRefGoogle Scholar
  19. Sandvig, K., Olsnes, S., Beterson, O.W., and van Deurs, B., 1987. Acidification of the cytosol inhibits endocytosis from coated pits. J. Cell Biol. 105:679–689.PubMedCrossRefGoogle Scholar
  20. Severs, N.J., 1988. Caveolae, static inpocketings of the plasma membrane, dynamic vesicles, or plain artifact? J. Cell Sci. 90:341–348.PubMedGoogle Scholar
  21. Simionescu, M., Simionescu, N., and Palade, G.E., 1982. Differentiated microdomains on the luminal surface of capillary endothelium: distribution of lectin receptors. J. Cell Biol. 94:406–413.PubMedCrossRefGoogle Scholar
  22. Smart, E.J., Foster, D.C., Ying, Y., Kamen, B.A., and Anderson, R.G.W., 1994. Protein kinase activators inhibit receptor-mediated potocytosis by preventing internalization of caveolae. J. Cell Biol. 124:307–313.PubMedCrossRefGoogle Scholar
  23. Tran, D., Carpenter, J.L., Sawano, F., Gorden, G., and Orci, L., 1987. Ligands internalized through coated or non-coated invaginations follow a common intracellulr pathway. Proc. Natl. Acad. Sci. USA 84:7947- 7961.CrossRefGoogle Scholar
  24. Varga, M.J., Weibull, C., and Everitt, E., 1991. Infectious entry pathway of adenovirus type 2. J. Virol. 65:6061–6070.PubMedGoogle Scholar
  25. Yewdell, J.W., and Bennink, J.R., 1992. Cell biology of antigen processing and presentation to major histocompatibility complex class I molecule-restricted T lymphocytes. Adv. Immunol. 52:1–124.PubMedCrossRefGoogle Scholar
  26. Zullo, J., Stiles, C.D., and Garcia, R.L., 1987. Regulation of c-myc and c-fos mRNA levels by polyomavirus: distinct roles for the capsid protein VP1 and the viral early proteins. Proc. Natl. Acad. Sci. USA 84:1210–1214.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1996

Authors and Affiliations

  • Leonard C. Norkin
    • 1
  • Howard A. Anderson
    • 2
  1. 1.Department of MicrobiologyUniversity of MassachusettsAmherstUSA
  2. 2.Experimental Immunology BranchNational Cancer InstituteBethesdaUSA

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