1887

Abstract

The Sindbis virus mutant NE2G216 retains PE2 in place of E2 in its virion structure. NE2G216 is a host-range mutant that replicates with near-normal kinetics in vertebrate cells, but displays severely restricted growth in cultured mosquito cells (C6/36) due to defects in the virus maturation process. In this study we tested the hypothesis that the host-range phenotype of NE2G216 was linked to the differences in carbohydrate-processing phenotypes between vertebrate and arthropod cells. Arthropod cell-derived glycoproteins are distinguishable from those synthesized in vertebrate cells by the absence of complex- and hybrid-type -linked oligosaccharides. To test our hypothesis we compared the growth of the wild-type virus, TRSB, NE2G216 and three PE2-containing, C6/36 cell-adapted variants, in vertebrate cells treated with 1-deoxymannojirimycin (1-dMM). 1-dMM inhibits the Golgi α-mannosidase I enzyme and limits oligosaccharide processing to high-mannose forms (ManGlcNAc). The growth of TRSB was not restricted by the action of 1-dMM; however, NE2G216 was restricted in a dose-dependent manner. In contrast, the growth of each PE2-containing, C6/36 cell-adapted mutant was enhanced by low concentrations of 1-dMM (up to 1500%) and was only slightly affected by the higher concentrations. These results demonstrate that virion maturation functions of NE2G216 are sensitive to the structure of -linked oligosaccharides, and indicate that the carbohydrate-processing phenotypes of the host cell can influence viral host-range and function as a selective pressure in alphavirus evolution.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-81-1-161
2000-01-01
2019-10-21
Loading full text...

Full text loading...

/deliver/fulltext/jgv/81/1/0810161a.html?itemId=/content/journal/jgv/10.1099/0022-1317-81-1-161&mimeType=html&fmt=ahah

References

  1. Balasuriya, U. B. R., Snijder, E. J., van Dinten, L. C., Heidner, H. W., Wilson, D. W., Hedges, J. F., Hullinger, P. J. & MacLachlan, N. J. ( 1999; ). Equine arteritis virus derived from an infectious cDNA clone is attenuated and genetically stable in infected stallions. Virology 260, 201-208.[CrossRef]
    [Google Scholar]
  2. Bischoff, J., Liscum, L. & Kornfeld, R. ( 1986; ). The use of 1-deoxymannojirimycin to evaluate the role of various α-mannosidases in oligosaccharide processing in intact cells. Journal of Biological Chemistry 261, 4766-4774.
    [Google Scholar]
  3. Bosch, J. V., Tlusty, A., McDowell, W., Legler, G. & Schwarz, R. T. ( 1985; ). The mannosidase inhibitors 1-deoxymannojirimycin and swainsonine have no effect on the biosynthesis and infectivity of Rous sarcoma virus. Virology 143, 342-346.[CrossRef]
    [Google Scholar]
  4. Burke, D. & Keegstra, K. ( 1979; ). Carbohydrate structure of Sindbis virus glycoprotein E2 from virus grown in hamster and chicken cells. Journal of Virology 29, 546-554.
    [Google Scholar]
  5. Butters, T. D. & Hughes, R. C. ( 1981; ). Isolation and characterization of mosquito cell membrane glycoproteins. Biochimica et Biophysica Acta 640, 655-671.[CrossRef]
    [Google Scholar]
  6. Butters, T. D., Hughes, R. C. & Vischer, P. ( 1981; ). Steps in the biosynthesis of mosquito cell membrane glycoproteins and the effects of tunicamycin. Biochimica et Biophysica Acta 640, 672-686.[CrossRef]
    [Google Scholar]
  7. Datema, R., Romero, P. A., Rott, R. & Schwarz, R. T. ( 1984; ). On the role of oligosaccharide trimming in the maturation of Sindbis and influenza virus. Archives of Virology 81, 25-39.[CrossRef]
    [Google Scholar]
  8. Davis, N. L., Brown, K. W., Greenwald, G. F., Zajac, A. J., Zacny, V. L., Smith, J. F. & Johnston, R. E. ( 1995; ). Attenuated mutants of Venezuelan equine encephalitis virus containing lethal mutations in the PE2 cleavage signal combined with a second-site suppressor mutation in E1. Virology 112, 102-110.
    [Google Scholar]
  9. Doms, R. W., Lamb, R. A., Rose, J. K. & Helenius, A. ( 1993; ). Folding and assembly of viral membrane proteins. Virology 193, 545-562.[CrossRef]
    [Google Scholar]
  10. Durbin, R. K. & Stollar, V. ( 1984; ). A mutant of Sindbis virus with a host-dependent defect in maturation associated with hyperglycosylation of E2. Virology 135, 331-344.[CrossRef]
    [Google Scholar]
  11. Durbin, R. K. & Stollar, V. ( 1986; ). Sequence analysis of the E2 gene of a hyperglycosylated, host restricted mutant of Sindbis virus and estimation of mutation rate from frequency of revertants. Virology 154, 135-143.[CrossRef]
    [Google Scholar]
  12. Elbein, A. D. ( 1987; ). Inhibitors of the biosynthesis and processing of N-linked oligosaccharide chains. Annual Review of Biochemistry 56, 497-534.[CrossRef]
    [Google Scholar]
  13. Elbein, A. D., Legler, G., Tlusty, A., McDowell, W. & Schwartz, R. ( 1984; ). The effect of deoxymannojirimycin on the processing of the influenza viral glycoproteins. Archives of Biochemistry and Biophysics 235, 579-588.[CrossRef]
    [Google Scholar]
  14. Fiedler, K. & Simons, K. ( 1995; ). The role of N-glycans in the secretory pathway. Cell 81, 309-312.[CrossRef]
    [Google Scholar]
  15. Fuhrmann, U., Bause, E., Legler, G. & Ploegh, H. ( 1984; ). Novel mannosidase inhibitor blocking conversion of high mannose to complex oligosaccharides. Nature 307, 755-758.[CrossRef]
    [Google Scholar]
  16. Gliedman, J. B., Smith, J. F. & Brown, D. T. ( 1975; ). Morphogenesis of Sindbis virus in cultured Aedes albopictus cells. Journal of Virology 16, 913-926.
    [Google Scholar]
  17. Gruters, R. A., Neefjes, J. J., Tersmette, M., de Goede, R. E. Y., Tulp, A., Huisman, H. G., Miedema, F. & Ploegh, H. L. ( 1987; ). Interference with HIV-induced syncytium formation and viral infectivity by inhibitors of trimming glucosidase. Nature 330, 74-77.[CrossRef]
    [Google Scholar]
  18. Heidner, H. W., McKnight, K. L., Davis, N. L. & Johnston, R. E. ( 1994; ). Lethality of PE2 incorporation into Sindbis virus can be suppressed by second-site mutations in E3 and E2. Journal of Virology 68, 2683-2692.
    [Google Scholar]
  19. Heidner, H. W., Knott, T. A. & Johnston, R. E. ( 1996; ). Differential processing of Sindbis virus glycoprotein PE2 in cultured vertebrate and arthropod cells. Journal of Virology 70, 2069-2073.
    [Google Scholar]
  20. Hsieh, P. & Robbins, P. W. ( 1984; ). Regulation of asparagine-linked oligosaccharide processing: oligosaccharide processing in Aedes albopictus mosquito cells. Journal of Biological Chemistry 259, 2375-2382.
    [Google Scholar]
  21. Hsieh, P., Rosner, M. R. & Robbins, P. W. ( 1983; ). Host-dependent variation of asparagine-linked oligosaccharides at individual glycosylation sites of Sindbis virus glycoproteins. Journal of Biological Chemistry 258, 2548-2554.
    [Google Scholar]
  22. Igarashi, A. ( 1978; ). Isolation of a Singh’s Aedes albopictus cell clone sensitive to Dengue and Chikungunya viruses. Journal of General Virology 40, 531-544.[CrossRef]
    [Google Scholar]
  23. Keegstra, K., Sefton, B. & Burke, D. ( 1975; ). Sindbis virus glycoproteins: effect of the host cell on the oligosaccharides. Journal of Virology 16, 613-620.
    [Google Scholar]
  24. Kornfeld, R. & Kornfeld, S. ( 1985; ). Assembly of asparagine-linked oligosaccharides. Annual Review of Biochemistry 54, 631-664.[CrossRef]
    [Google Scholar]
  25. Laemmli, U. K. ( 1970; ). Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227, 680-685.[CrossRef]
    [Google Scholar]
  26. McDowell, W., Romero, P. A., Datema, R. & Schwarz, R. T. ( 1987; ). Glucose trimming and mannose trimming affect different phases of the maturation of Sindbis virus in infected BHK cells. Virology 161, 37-44.[CrossRef]
    [Google Scholar]
  27. McKnight, K. L., Simpson, D. A., Lin, S. C., Knott, T. A., Polo, J. M., Pence, D. F., Johannsen, D. B., Heidner, H. W., Davis, N. L. & Johnston, R. E. ( 1996; ). Deduced consensus sequence of Sindbis virus strain AR339: mutations contained in laboratory strains which affect cell culture and in vivo phenotypes. Journal of Virology 70, 1981-1989.
    [Google Scholar]
  28. März, L., Altmann, F., Staudacher, E. & Kubelka, V. ( 1995; ). Protein glycosylation in insects. In Glycoproteins, pp. 543-563. Edited by J. Montreuil, J. F. G. Vliegenthart & H. Schachter. Amsterdam: Elsevier.
  29. Mayne, J. T., Bell, J. R., Strauss, E. G. & Strauss, J. H. ( 1985; ). Pattern of glycosylation of Sindbis virus envelope proteins synthesized in hamster and chicken cells. Virology 142, 121-133.[CrossRef]
    [Google Scholar]
  30. Miller, M. L. & Brown, D. T. ( 1992; ). Morphogenesis of Sindbis virus in three subclones of Aedes albopictus (mosquito) cells. Journal of Virology 66, 4180-4190.
    [Google Scholar]
  31. Naim, H. Y. & Koblet, K. ( 1988; ). Investigation of the role of glycans for the biological activity of Semliki Forest virus grown in Aedes albopictus cells using inhibitors of asparagine-linked oligosaccharide trimming. Archives of Virology 102, 73-89.[CrossRef]
    [Google Scholar]
  32. Paredes, A. M., Heidner, H. W., Thuman-Commike, P., Prasad, B. V. V., Johnston, R. E. & Chiu, W. ( 1998; ). Structural localization of the E3 glycoprotein in attenuated Sindbis virus mutants. Journal of Virology 72, 1534-1541.
    [Google Scholar]
  33. Presley, J. F., Polo, J. M., Johnston, R. E. & Brown, D. T. ( 1991; ). Proteolytic processing of the Sindbis virus membrane protein precursor PE2 is nonessential for growth in vertebrate cells but is required for efficient growth in invertebrate cells. Journal of Virology 65, 1905-1909.
    [Google Scholar]
  34. Repp, R., Tamura, T., Boschek, C. B., Wegel, H., Schwarz, R. T. & Niemann, H. ( 1985; ). The effects of processing inhibitors of N-linked oligosaccharides on the intracellular migration of glycoprotein E2 of mouse hepatitis virus and the maturation of coronavirus particles. Journal of Biological Chemistry 260, 15873-15879.
    [Google Scholar]
  35. Rice, C. M. & Strauss, J. H. ( 1981; ). Nucleotide sequence of the 26S mRNA of Sindbis virus and deduced sequence of the encoded virus structural proteins. Proceedings of the National Academy of Sciences, USA 28, 2062-2066.
    [Google Scholar]
  36. Russell, D. L., Dalrymple, J. M. & Johnston, R. E. ( 1989; ). Sindbis virus mutations which coordinately affect glycoprotein processing, penetration, and virulence in mice. Journal of Virology 63, 1619-1629.
    [Google Scholar]
  37. Salminen, A., Wahlberg, J. M., Lobigs, M., Liljeström, P. & Garoff, H. ( 1992; ). Membrane fusion process of Semliki Forest virus II: cleavage-dependent reorganization of the spike protein complex controls virus entry. Journal of Cell Biology 116, 349-357.[CrossRef]
    [Google Scholar]
  38. Schlesinger, S., Koyama, A. H., Malfer, C., Gee, S. L. & Schlesinger, M. J. ( 1985; ). The effects of inhibitors of glucosidase I on the formation of Sindbis virus. Virus Research 2, 139-149.[CrossRef]
    [Google Scholar]
  39. Stollar, V. & Hardy, J. L. ( 1984; ). Host-dependent mutants of Sindbis virus whose growth is restricted in cultured Aedes albopictus cells produce normal yields of virus in intact mosquitos. Virology 134, 177-183.[CrossRef]
    [Google Scholar]
  40. Stollar, V., Stollar, B. D., Koo, R., Harrap, K. A. & Schlesinger, R. W. ( 1976; ). Sialic acid content of Sindbis virus from vertebrate and mosquito cells: equivalence of biological and immunological viral properties. Virology 69, 104-115.[CrossRef]
    [Google Scholar]
  41. Strauss, J. H. & Strauss, E. G. ( 1994; ). The alphaviruses: gene expression, replication, and evolution. Microbiological Reviews 58, 491-562.
    [Google Scholar]
  42. Tubulekas, I. & Liljeström, P. ( 1998; ). Suppressors of cleavage-site mutations in the p62 envelope protein of Semliki Forest virus reveal dynamics in spike structure and function. Journal of Virology 72, 2825-2831.
    [Google Scholar]
  43. Weaver, S. C., Brault, A. C., Kang, W. & Holland, J. J. ( 1999; ). Genetic and fitness changes accompanying adaptation of an arbovirus to vertebrate and invertebrate cells. Journal of Virology 73, 4316-4326.
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-81-1-161
Loading
/content/journal/jgv/10.1099/0022-1317-81-1-161
Loading

Data & Media loading...

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error