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Viral Determinants of Age-Dependent Virulence of Sindbis Virus for Mice

Tucker, Pamela C. and Strauss, Ellen G. and Kuhn, Richard J. and Strauss, James H. and Griffin, Diane E. (1993) Viral Determinants of Age-Dependent Virulence of Sindbis Virus for Mice. Journal of Virology, 67 (8). pp. 4605-4610. ISSN 0022-538X. PMCID PMC237845.

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Many alphaviruses cause more severe disease in young animals than in older animals. The age-dependent resistance to severe disease is determined primarily by maturation of the host, but strains of virus can be selected that overcome the increased resistance of mature animals. Sindbis virus (SV) strain AR339 causes fatal encephalitis in newborn mice and nonfatal encephalitis in weanling mice, whereas NSV, a neuroadapted strain of SV, causes fatal encephalitis in weanling as well as newborn mice. We have previously shown that the E2 glycoprotein of NSV contained His-55, whereas AR339 E2 had Gln-55 (S. Lustig, A. C. Jackson, C. S. Hahn, D. E. Griffin, E. G. Strauss, and J. H. Strauss, J. Virol. 62:2329-2336, 1988) and that SV with E2 containing Gly-172 was more virulent for newborn mice than SV with E2 containing Arg-172 (P. C. Tucker and D. E. Griffin, J. Virol. 65:1551-1557, 1991). Here we tested the vinrlence for both newborn and older mice of SV containing a number of different amino acids at E2 position 55 (His, Gln, Lys, Arg, Glu, Gly) in combination with both Gly-172 and Arg-172. All the viruses were virulent for newborn mice, but the residues at both 55 and 172 influenced the virulence of the virus, and there were differences in virulence observed among the various viruses. However, only viruses with His-55 were fully virulent for 14-day-old mice, and this virulence was independent of the residue at position 172. Virus with Lys-55 was virulent for 7-day-old mice, although slightly attenuated relative to His-55. Viruses with His-55 grew more rapidly and to higher titer in the brains of 7- and 14-day-old mice, in N18 neuroblastoma cells, and in BHK cells. Our data suggest that His-55 is important for neurovinrulence in older mice and acts by increasing the efficiency of virus replication.

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Additional Information:© 1993 American Society for Microbiology. Received 16 November 1992/Accepted 26 April 1993. This work was supported by Public Health Service grants NS18596 (D.E.G.), AI01070-01 (P.C.T.), and AI10793 (J.H.S.). We appreciate the contnbutions of Cameron Crandall and Tish Nance-Sporson for statistical assistance, Marcia Lyons for technical assistance, and Kimberley Collins for manuscript preparation.
Funding AgencyGrant Number
NIHNS 18596
NIHAI 01070-01
NIHAI 10793
Issue or Number:8
PubMed Central ID:PMC237845
Record Number:CaltechAUTHORS:20160411-161010078
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:66062
Deposited By: Donna Wrublewski
Deposited On:12 Apr 2016 21:05
Last Modified:03 Oct 2019 09:53

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