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. 1996 Feb;70(2):1255–1260. doi: 10.1128/jvi.70.2.1255-1260.1996

Effect of E2 envelope glycoprotein cytoplasmic domain mutations on Sindbis virus pathogenesis.

B Levine 1, H H Jiang 1, L Kleeman 1, G Yang 1
PMCID: PMC189939  PMID: 8551591

Abstract

The cytoplasmic domain of the E2 envelope glycoprotein is important in Sindbis virus assembly, but little is known about its role in the pathogenesis of Sindbis virus encephalitis. To investigate its role in viral pathogenesis, we constructed six recombinant viruses containing site mutations in the E2 cytoplasmic domain, using the neurovirulent background strain, TE12. Our findings demonstrate that the E2 cytoplasmic domain is a determinant of Sindbis virus growth and neurovirulence in suckling mice as well as persistent infection in weanling scid mice. They also suggest that the tyrosine, serine, or threonine residues are not essential for replication in mouse brain or anti-E2 monoclonal antibody-mediated restriction of Sindbis virus replication.

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Selected References

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  1. Davis N. L., Fuller F. J., Dougherty W. G., Olmsted R. A., Johnston R. E. A single nucleotide change in the E2 glycoprotein gene of Sindbis virus affects penetration rate in cell culture and virulence in neonatal mice. Proc Natl Acad Sci U S A. 1986 Sep;83(18):6771–6775. doi: 10.1073/pnas.83.18.6771. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Gaedigk-Nitschko K., Schlesinger M. J. Site-directed mutations in Sindbis virus E2 glycoprotein's cytoplasmic domain and the 6K protein lead to similar defects in virus assembly and budding. Virology. 1991 Jul;183(1):206–214. doi: 10.1016/0042-6822(91)90133-v. [DOI] [PubMed] [Google Scholar]
  3. Griffin D. E. Molecular pathogenesis of Sindbis virus encephalitis in experimental animals. Adv Virus Res. 1989;36:255–271. doi: 10.1016/s0065-3527(08)60587-4. [DOI] [PubMed] [Google Scholar]
  4. Heidner H. W., Johnston R. E. The amino-terminal residue of Sindbis virus glycoprotein E2 influences virus maturation, specific infectivity for BHK cells, and virulence in mice. J Virol. 1994 Dec;68(12):8064–8070. doi: 10.1128/jvi.68.12.8064-8070.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Hertz J. M., Huang H. V. Utilization of heterologous alphavirus junction sequences as promoters by Sindbis virus. J Virol. 1992 Feb;66(2):857–864. doi: 10.1128/jvi.66.2.857-864.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Ivanova L., Lustig S., Schlesinger M. J. A pseudo-revertant of a Sindbis virus 6K protein mutant, which corrects for aberrant particle formation, contains two new mutations that map to the ectodomain of the E2 glycoprotein. Virology. 1995 Feb 1;206(2):1027–1034. doi: 10.1006/viro.1995.1025. [DOI] [PubMed] [Google Scholar]
  7. Ivanova L., Schlesinger M. J. Site-directed mutations in the Sindbis virus E2 glycoprotein identify palmitoylation sites and affect virus budding. J Virol. 1993 May;67(5):2546–2551. doi: 10.1128/jvi.67.5.2546-2551.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Kail M., Hollinshead M., Ansorge W., Pepperkok R., Frank R., Griffiths G., Vaux D. The cytoplasmic domain of alphavirus E2 glycoprotein contains a short linear recognition signal required for viral budding. EMBO J. 1991 Sep;10(9):2343–2351. doi: 10.1002/j.1460-2075.1991.tb07773.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Levine B., Griffin D. E. Molecular analysis of neurovirulent strains of Sindbis virus that evolve during persistent infection of scid mice. J Virol. 1993 Nov;67(11):6872–6875. doi: 10.1128/jvi.67.11.6872-6875.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Levine B., Hardwick J. M., Trapp B. D., Crawford T. O., Bollinger R. C., Griffin D. E. Antibody-mediated clearance of alphavirus infection from neurons. Science. 1991 Nov 8;254(5033):856–860. doi: 10.1126/science.1658936. [DOI] [PubMed] [Google Scholar]
  11. Liu N., Brown D. T. Phosphorylation and dephosphorylation events play critical roles in Sindbis virus maturation. Virology. 1993 Oct;196(2):703–711. doi: 10.1006/viro.1993.1527. [DOI] [PubMed] [Google Scholar]
  12. Lopez S., Yao J. S., Kuhn R. J., Strauss E. G., Strauss J. H. Nucleocapsid-glycoprotein interactions required for assembly of alphaviruses. J Virol. 1994 Mar;68(3):1316–1323. doi: 10.1128/jvi.68.3.1316-1323.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Lustig S., Halevy M., Ben-Nathan D., Akov Y. A novel variant of Sindbis virus is both neurovirulent and neuroinvasive in adult mice. Arch Virol. 1992;122(3-4):237–248. doi: 10.1007/BF01317186. [DOI] [PubMed] [Google Scholar]
  14. Lustig S., Jackson A. C., Hahn C. S., Griffin D. E., Strauss E. G., Strauss J. H. Molecular basis of Sindbis virus neurovirulence in mice. J Virol. 1988 Jul;62(7):2329–2336. doi: 10.1128/jvi.62.7.2329-2336.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Metsikkö K., Garoff H. Oligomers of the cytoplasmic domain of the p62/E2 membrane protein of Semliki Forest virus bind to the nucleocapsid in vitro. J Virol. 1990 Oct;64(10):4678–4683. doi: 10.1128/jvi.64.10.4678-4683.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Olmsted R. A., Meyer W. J., Johnston R. E. Characterization of Sindbis virus epitopes important for penetration in cell culture and pathogenesis in animals. Virology. 1986 Jan 30;148(2):245–254. doi: 10.1016/0042-6822(86)90322-3. [DOI] [PubMed] [Google Scholar]
  17. Polo J. M., Davis N. L., Rice C. M., Huang H. V., Johnston R. E. Molecular analysis of Sindbis virus pathogenesis in neonatal mice by using virus recombinants constructed in vitro. J Virol. 1988 Jun;62(6):2124–2133. doi: 10.1128/jvi.62.6.2124-2133.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Polo J. M., Johnston R. E. Attenuating mutations in glycoproteins E1 and E2 of Sindbis virus produce a highly attenuated strain when combined in vitro. J Virol. 1990 Sep;64(9):4438–4444. doi: 10.1128/jvi.64.9.4438-4444.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Polo J. M., Johnston R. E. Mutational analysis of a virulence locus in the E2 glycoprotein gene of Sindbis virus. J Virol. 1991 Nov;65(11):6358–6361. doi: 10.1128/jvi.65.11.6358-6361.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Rice C. M., Strauss J. H. Nucleotide sequence of the 26S mRNA of Sindbis virus and deduced sequence of the encoded virus structural proteins. Proc Natl Acad Sci U S A. 1981 Apr;78(4):2062–2066. doi: 10.1073/pnas.78.4.2062. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Schmaljohn A. L., Johnson E. D., Dalrymple J. M., Cole G. A. Non-neutralizing monoclonal antibodies can prevent lethal alphavirus encephalitis. Nature. 1982 May 6;297(5861):70–72. doi: 10.1038/297070a0. [DOI] [PubMed] [Google Scholar]
  23. Schoepp R. J., Johnston R. E. Directed mutagenesis of a Sindbis virus pathogenesis site. Virology. 1993 Mar;193(1):149–159. doi: 10.1006/viro.1993.1111. [DOI] [PubMed] [Google Scholar]
  24. Strauss J. H., Strauss E. G. The alphaviruses: gene expression, replication, and evolution. Microbiol Rev. 1994 Sep;58(3):491–562. doi: 10.1128/mr.58.3.491-562.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Tucker P. C., Griffin D. E. Mechanism of altered Sindbis virus neurovirulence associated with a single-amino-acid change in the E2 Glycoprotein. J Virol. 1991 Mar;65(3):1551–1557. doi: 10.1128/jvi.65.3.1551-1557.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Tucker P. C., Strauss E. G., Kuhn R. J., Strauss J. H., Griffin D. E. Viral determinants of age-dependent virulence of Sindbis virus for mice. J Virol. 1993 Aug;67(8):4605–4610. doi: 10.1128/jvi.67.8.4605-4610.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Ubol S., Griffin D. E. Identification of a putative alphavirus receptor on mouse neural cells. J Virol. 1991 Dec;65(12):6913–6921. doi: 10.1128/jvi.65.12.6913-6921.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Ubol S., Levine B., Lee S. H., Greenspan N. S., Griffin D. E. Roles of immunoglobulin valency and the heavy-chain constant domain in antibody-mediated downregulation of Sindbis virus replication in persistently infected neurons. J Virol. 1995 Mar;69(3):1990–1993. doi: 10.1128/jvi.69.3.1990-1993.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Wang K. S., Schmaljohn A. L., Kuhn R. J., Strauss J. H. Antiidiotypic antibodies as probes for the Sindbis virus receptor. Virology. 1991 Apr;181(2):694–702. doi: 10.1016/0042-6822(91)90903-o. [DOI] [PubMed] [Google Scholar]
  30. Zhao H., Lindqvist B., Garoff H., von Bonsdorff C. H., Liljeström P. A tyrosine-based motif in the cytoplasmic domain of the alphavirus envelope protein is essential for budding. EMBO J. 1994 Sep 15;13(18):4204–4211. doi: 10.1002/j.1460-2075.1994.tb06740.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

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