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. 1993 Nov;67(11):6872–6875. doi: 10.1128/jvi.67.11.6872-6875.1993

Molecular analysis of neurovirulent strains of Sindbis virus that evolve during persistent infection of scid mice.

B Levine 1, D E Griffin 1
PMCID: PMC238135  PMID: 8411391

Abstract

To understand the role of tissue-specific adaptation and antibody-induced selectional pressures in the evolution of neurovirulent viruses, we analyzed three strains of Sindbis virus isolated from the brains of persistently infected scid mice and four strains of Sindbis virus isolated from the brains of scid mice with viral reactivation following immune serum treatment. For each viral isolate, we tested neurovirulence in weanling BALB/c mice and sequenced regions of the E2 and E1 envelope glycoprotein genes that are known to contain important determinants of Sindbis virus neurovirulence. One strain isolated from a persistently infected scid mouse and two strains isolated from scid mice with viral reactivation were neurovirulent, resulting in mortality in 80 to 100% of weanling BALB/c mice. All three neurovirulent strains contained an A-->U change at nucleotide 8795, which predicts a Gln-->His substitution at E2 amino acid position 55. No nucleotide changes were detected in the other sequenced regions of the E2 and E1 envelope glycoprotein genes or in the avirulent isolates. Our findings indicate that tissue-specific adaptations, rather than antibody-induced selectional pressures, are a critical determinant of the evolution of neurovirulent strains of Sindbis virus and provide evidence that E2 His-55 is an important neuroadaptive mutation that confers neurovirulence properties on Sindbis virus.

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Selected References

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  1. Ahmed R., Hahn C. S., Somasundaram T., Villarete L., Matloubian M., Strauss J. H. Molecular basis of organ-specific selection of viral variants during chronic infection. J Virol. 1991 Aug;65(8):4242–4247. doi: 10.1128/jvi.65.8.4242-4247.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Ahmed R., Oldstone M. B. Organ-specific selection of viral variants during chronic infection. J Exp Med. 1988 May 1;167(5):1719–1724. doi: 10.1084/jem.167.5.1719. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. 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]
  4. Griffin D. E., Johnson R. T. Role of the immune response in recovery from Sindbis virus encephalitis in mice. J Immunol. 1977 Mar;118(3):1070–1075. [PubMed] [Google Scholar]
  5. 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]
  6. Hahn B. H., Shaw G. M., Taylor M. E., Redfield R. R., Markham P. D., Salahuddin S. Z., Wong-Staal F., Gallo R. C., Parks E. S., Parks W. P. Genetic variation in HTLV-III/LAV over time in patients with AIDS or at risk for AIDS. Science. 1986 Jun 20;232(4757):1548–1553. doi: 10.1126/science.3012778. [DOI] [PubMed] [Google Scholar]
  7. Koyanagi Y., Miles S., Mitsuyasu R. T., Merrill J. E., Vinters H. V., Chen I. S. Dual infection of the central nervous system by AIDS viruses with distinct cellular tropisms. Science. 1987 May 15;236(4803):819–822. doi: 10.1126/science.3646751. [DOI] [PubMed] [Google Scholar]
  8. Levine B., Griffin D. E. Persistence of viral RNA in mouse brains after recovery from acute alphavirus encephalitis. J Virol. 1992 Nov;66(11):6429–6435. doi: 10.1128/jvi.66.11.6429-6435.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. 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]
  10. Levine B., Huang Q., Isaacs J. T., Reed J. C., Griffin D. E., Hardwick J. M. Conversion of lytic to persistent alphavirus infection by the bcl-2 cellular oncogene. Nature. 1993 Feb 25;361(6414):739–742. doi: 10.1038/361739a0. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. 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]
  13. Pang S., Vinters H. V., Akashi T., O'Brien W. A., Chen I. S. HIV-1 env sequence variation in brain tissue of patients with AIDS-related neurologic disease. J Acquir Immune Defic Syndr. 1991;4(11):1082–1092. [PubMed] [Google Scholar]
  14. 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]
  15. 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]
  16. Rice C. M., Bell J. R., Hunkapiller M. W., Strauss E. G., Strauss J. H. Isolation and characterization of the hydrophobic COOH-terminal domains of the sindbis virion glycoproteins. J Mol Biol. 1982 Jan 15;154(2):355–378. doi: 10.1016/0022-2836(82)90069-9. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. Saag M. S., Hahn B. H., Gibbons J., Li Y., Parks E. S., Parks W. P., Shaw G. M. Extensive variation of human immunodeficiency virus type-1 in vivo. Nature. 1988 Aug 4;334(6181):440–444. doi: 10.1038/334440a0. [DOI] [PubMed] [Google Scholar]
  19. 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]
  20. Strauss E. G., Stec D. S., Schmaljohn A. L., Strauss J. H. Identification of antigenically important domains in the glycoproteins of Sindbis virus by analysis of antibody escape variants. J Virol. 1991 Sep;65(9):4654–4664. doi: 10.1128/jvi.65.9.4654-4664.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. TAYLOR R. M., HURLBUT H. S. The isolation of Coxsackie-like viruses from mosquitoes. J Egypt Med Assoc. 1953;36(9):489–494. [PubMed] [Google Scholar]
  22. TAYLOR R. M., HURLBUT H. S., WORK T. H., KINGSTON J. R., FROTHINGHAM T. E. Sindbis virus: a newly recognized arthropodtransmitted virus. Am J Trop Med Hyg. 1955 Sep;4(5):844–862. doi: 10.4269/ajtmh.1955.4.844. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. 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]
  25. 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]
  26. 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]

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