Molecular basis of Sindbis virus neurovirulence in mice.
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Journal: 1988/July - Journal of Virology
ISSN: 0022-538X
PUBMED: 2836615
Abstract:
We examined a variety of strains of Sindbis virus for the genetic changes responsible for differences in neurovirulence in mice. SV1A (a low passage of the AR339 strain of Sindbis virus), a neuroadapted Sindbis virus (NSV), and two laboratory strains of Sindbis virus (HRSP and Toto1101) were examined. NSV causes severe encephalomyelitis with hind-limb paralysis and high mortality after intracerebral inoculation in weanling mice. In contrast, SV1A causes only mild, nonfatal disease in weanling mice; however, in suckling mice, SV1A causes a fatal encephalomyelitis after either intracerebral or subcutaneous inoculation. The two laboratory strains used have a greatly reduced neurovirulence for suckling mice and are avirulent for weanling mice. The nucleotide sequences and encoded amino acid sequences of the structural glycoproteins of these four strains were compared. Hybrid genomes were constructed by replacing restriction fragments in a full-length cDNA clone of Sindbis virus, from which infectious RNA can be transcribed in vitro, with fragments from cDNA clones of the various strains. These recombinant viruses allowed us to test the importance of each amino acid difference between the various strains for neurovirulence in weanling and suckling mice. Glycoproteins E2 and E1 were of paramount importance for neurovirulence in adult mice. Recombinant viruses containing the nonstructural protein region and the capsid protein region from an avirulent strain and the E1 and E2 glycoprotein regions from NSV were virulent, although they were less virulent than NSV. Furthermore, changes in either E2 (His-55 in NSV to Gln in SV1A) or E1 (Ala-72 in NSV to Val in SV1A and Asp-313 in NSV to Gly in SV1A) reduced virulence. For virulence in suckling mice, we found that a number of changes in E2 and E1 can lead to decreased virulence and that in fact, a gradient of virulence exists.
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J Virol 62(7): 2329-2336
PMID: 2836615

Molecular basis of Sindbis virus neurovirulence in mice.

Abstract

We examined a variety of strains of Sindbis virus for the genetic changes responsible for differences in neurovirulence in mice. SV1A (a low passage of the AR339 strain of Sindbis virus), a neuroadapted Sindbis virus (NSV), and two laboratory strains of Sindbis virus (HRSP and Toto1101) were examined. NSV causes severe encephalomyelitis with hind-limb paralysis and high mortality after intracerebral inoculation in weanling mice. In contrast, SV1A causes only mild, nonfatal disease in weanling mice; however, in suckling mice, SV1A causes a fatal encephalomyelitis after either intracerebral or subcutaneous inoculation. The two laboratory strains used have a greatly reduced neurovirulence for suckling mice and are avirulent for weanling mice. The nucleotide sequences and encoded amino acid sequences of the structural glycoproteins of these four strains were compared. Hybrid genomes were constructed by replacing restriction fragments in a full-length cDNA clone of Sindbis virus, from which infectious RNA can be transcribed in vitro, with fragments from cDNA clones of the various strains. These recombinant viruses allowed us to test the importance of each amino acid difference between the various strains for neurovirulence in weanling and suckling mice. Glycoproteins E2 and E1 were of paramount importance for neurovirulence in adult mice. Recombinant viruses containing the nonstructural protein region and the capsid protein region from an avirulent strain and the E1 and E2 glycoprotein regions from NSV were virulent, although they were less virulent than NSV. Furthermore, changes in either E2 (His-55 in NSV to Gln in SV1A) or E1 (Ala-72 in NSV to Val in SV1A and Asp-313 in NSV to Gly in SV1A) reduced virulence. For virulence in suckling mice, we found that a number of changes in E2 and E1 can lead to decreased virulence and that in fact, a gradient of virulence exists.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Arias C, Bell JR, Lenches EM, Strauss EG, Strauss JH. Sequence analysis of two mutants of Sindbis virus defective in the intracellular transport of their glycoproteins. J Mol Biol. 1983 Jul 25;168(1):87–102. [PubMed] [Google Scholar]
  • Barrett PN, Atkins GJ. Virulence of temperature-sensitive mutants of Sindbis virus in neonatal mice. Infect Immun. 1979 Dec;26(3):848–852.[PMC free article] [PubMed] [Google Scholar]
  • Bassel-Duby R, Spriggs DR, Tyler KL, Fields BN. Identification of attenuating mutations on the reovirus type 3 S1 double-stranded RNA segment with a rapid sequencing technique. J Virol. 1986 Oct;60(1):64–67.[PMC free article] [PubMed] [Google Scholar]
  • Beaty BJ, Holterman M, Tabachnick W, Shope RE, Rozhon EJ, Bishop DH. Molecular basis of bunyavirus transmission by mosquitoes: role of the middle-sized RNA segment. Science. 1981 Mar 27;211(4489):1433–1435. [PubMed] [Google Scholar]
  • Burge BW, Pfefferkorn ER. Isolation and characterization of conditional-lethal mutants of Sindbis virus. Virology. 1966 Oct;30(2):204–213. [PubMed] [Google Scholar]
  • Davis NL, Fuller FJ, Dougherty WG, Olmsted RA, Johnston RE. 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.[PMC free article] [PubMed] [Google Scholar]
  • EAGLE H. Amino acid metabolism in mammalian cell cultures. Science. 1959 Aug 21;130(3373):432–437. [PubMed] [Google Scholar]
  • Fuller SD. The T=4 envelope of Sindbis virus is organized by interactions with a complementary T=3 capsid. Cell. 1987 Mar 27;48(6):923–934. [PubMed] [Google Scholar]
  • Griffin DE. Role of the immune response in age-dependent resistance of mice to encephalitis due to Sindbis virus. J Infect Dis. 1976 Apr;133(4):456–464. [PubMed] [Google Scholar]
  • Griffin DE, Johnson RT. Role of the immune response in recovery from Sindbis virus encephalitis in mice. J Immunol. 1977 Mar;118(3):1070–1075. [PubMed] [Google Scholar]
  • Jackson AC, Moench TR, Griffin DE, Johnson RT. The pathogenesis of spinal cord involvement in the encephalomyelitis of mice caused by neuroadapted Sindbis virus infection. Lab Invest. 1987 Apr;56(4):418–423. [PubMed] [Google Scholar]
  • JOHNSON RT. VIRUS INVASION OF THE CENTRAL NERVOUS SYSTEM: A STUDY OF SINDBIS VIRUS INFECTION IN THE MOUSE USING FLUORESCENT ANTIBODY. Am J Pathol. 1965 Jun;46:929–943.[PMC free article] [PubMed] [Google Scholar]
  • Johnson RT, McFarland HF, Levy SE. Age-dependent resistance to viral encephalitis: studies of infections due to Sindbis virus in mice. J Infect Dis. 1972 Mar;125(3):257–262. [PubMed] [Google Scholar]
  • Kohara M, Omata T, Kameda A, Semler BL, Itoh H, Wimmer E, Nomoto A. In vitro phenotypic markers of a poliovirus recombinant constructed from infectious cDNA clones of the neurovirulent Mahoney strain and the attenuated Sabin 1 strain. J Virol. 1985 Mar;53(3):786–792.[PMC free article] [PubMed] [Google Scholar]
  • Lindqvist BH, DiSalvo J, Rice CM, Strauss JH, Strauss EG. Sindbis virus mutant ts20 of complementation group E contains a lesion in glycoprotein E2. Virology. 1986 May;151(1):10–20. [PubMed] [Google Scholar]
  • Maxam AM, Gilbert W. Sequencing end-labeled DNA with base-specific chemical cleavages. Methods Enzymol. 1980;65(1):499–560. [PubMed] [Google Scholar]
  • Okayama H, Berg P. High-efficiency cloning of full-length cDNA. Mol Cell Biol. 1982 Feb;2(2):161–170.[PMC free article] [PubMed] [Google Scholar]
  • Olmsted RA, Baric RS, Sawyer BA, Johnston RE. Sindbis virus mutants selected for rapid growth in cell culture display attenuated virulence in animals. Science. 1984 Jul 27;225(4660):424–427. [PubMed] [Google Scholar]
  • Olmsted RA, Meyer WJ, Johnston RE. Characterization of Sindbis virus epitopes important for penetration in cell culture and pathogenesis in animals. Virology. 1986 Jan 30;148(2):245–254. [PubMed] [Google Scholar]
  • Ou JH, Trent DW, Strauss JH. The 3'-non-coding regions of alphavirus RNAs contain repeating sequences. J Mol Biol. 1982 Apr 25;156(4):719–730. [PubMed] [Google Scholar]
  • Pierce JS, Strauss EG, Strauss JH. Effect of ionic strength on the binding of Sindbis virus to chick cells. J Virol. 1974 May;13(5):1030–1036.[PMC free article] [PubMed] [Google Scholar]
  • Polo JM, Davis NL, Rice CM, Huang HV, Johnston RE. Molecular analysis of Sindbis virus pathogenesis in neonatal mice by using virus recombinants constructed in vitro. J Virol. 1988 Jun;62(6):2124–2133.[PMC free article] [PubMed] [Google Scholar]
  • Reinarz AB, Broome MG, Sagik BP. Age-dependent resistance of mice to sindbis virus infection: viral replication as a function of host age. Infect Immun. 1971 Feb;3(2):268–273.[PMC free article] [PubMed] [Google Scholar]
  • Rice CM, Bell JR, Hunkapiller MW, Strauss EG, Strauss JH. Isolation and characterization of the hydrophobic COOH-terminal domains of the sindbis virion glycoproteins. J Mol Biol. 1982 Jan 15;154(2):355–378. [PubMed] [Google Scholar]
  • Rice CM, Levis R, Strauss JH, Huang HV. Production of infectious RNA transcripts from Sindbis virus cDNA clones: mapping of lethal mutations, rescue of a temperature-sensitive marker, and in vitro mutagenesis to generate defined mutants. J Virol. 1987 Dec;61(12):3809–3819.[PMC free article] [PubMed] [Google Scholar]
  • Rice CM, Strauss JH. Synthesis, cleavage and sequence analysis of DNA complementary to the 26 S messenger RNA of Sindbis virus. J Mol Biol. 1981 Aug 15;150(3):315–340. [PubMed] [Google Scholar]
  • Rice CM, Strauss JH. Association of sindbis virion glycoproteins and their precursors. J Mol Biol. 1982 Jan 15;154(2):325–348. [PubMed] [Google Scholar]
  • Seif I, Coulon P, Rollin PE, Flamand A. Rabies virulence: effect on pathogenicity and sequence characterization of rabies virus mutations affecting antigenic site III of the glycoprotein. J Virol. 1985 Mar;53(3):926–934.[PMC free article] [PubMed] [Google Scholar]
  • Smith AL, Tignor GH. Host cell receptors for two strains of Sindbis virus. Arch Virol. 1980;66(1):11–26. [PubMed] [Google Scholar]
  • Stanley J, Cooper SJ, Griffin DE. Alphavirus neurovirulence: monoclonal antibodies discriminating wild-type from neuroadapted Sindbis virus. J Virol. 1985 Oct;56(1):110–119.[PMC free article] [PubMed] [Google Scholar]
  • Strauss EG, Lenches EM, Strauss JH. Mutants of sindbis virus. I. Isolation and partial characterization of 89 new temperature-sensitive mutants. Virology. 1976 Oct 1;74(1):154–168. [PubMed] [Google Scholar]
  • Strauss EG, Rice CM, Strauss JH. Complete nucleotide sequence of the genomic RNA of Sindbis virus. Virology. 1984 Feb;133(1):92–110. [PubMed] [Google Scholar]
  • TAYLOR RM, HURLBUT HS, WORK TH, KINGSTON JR, FROTHINGHAM TE. Sindbis virus: a newly recognized arthropodtransmitted virus. Am J Trop Med Hyg. 1955 Sep;4(5):844–862. [PubMed] [Google Scholar]
  • Zimmern D, Kaesberg P. 3'-terminal nucleotide sequence of encephalomyocarditis virus RNA determined by reverse transcriptase and chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1978 Sep;75(9):4257–4261.[PMC free article] [PubMed] [Google Scholar]
Division of Biology, California Institute of Technology, Pasadena 91125.
Division of Biology, California Institute of Technology, Pasadena 91125.
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Abstract
We examined a variety of strains of Sindbis virus for the genetic changes responsible for differences in neurovirulence in mice. SV1A (a low passage of the AR339 strain of Sindbis virus), a neuroadapted Sindbis virus (NSV), and two laboratory strains of Sindbis virus (HRSP and Toto1101) were examined. NSV causes severe encephalomyelitis with hind-limb paralysis and high mortality after intracerebral inoculation in weanling mice. In contrast, SV1A causes only mild, nonfatal disease in weanling mice; however, in suckling mice, SV1A causes a fatal encephalomyelitis after either intracerebral or subcutaneous inoculation. The two laboratory strains used have a greatly reduced neurovirulence for suckling mice and are avirulent for weanling mice. The nucleotide sequences and encoded amino acid sequences of the structural glycoproteins of these four strains were compared. Hybrid genomes were constructed by replacing restriction fragments in a full-length cDNA clone of Sindbis virus, from which infectious RNA can be transcribed in vitro, with fragments from cDNA clones of the various strains. These recombinant viruses allowed us to test the importance of each amino acid difference between the various strains for neurovirulence in weanling and suckling mice. Glycoproteins E2 and E1 were of paramount importance for neurovirulence in adult mice. Recombinant viruses containing the nonstructural protein region and the capsid protein region from an avirulent strain and the E1 and E2 glycoprotein regions from NSV were virulent, although they were less virulent than NSV. Furthermore, changes in either E2 (His-55 in NSV to Gln in SV1A) or E1 (Ala-72 in NSV to Val in SV1A and Asp-313 in NSV to Gly in SV1A) reduced virulence. For virulence in suckling mice, we found that a number of changes in E2 and E1 can lead to decreased virulence and that in fact, a gradient of virulence exists.
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