1887

Abstract

Natural resistance to flaviviruses in mice is controlled by a single genetic locus, , on chromosome 5. Although the mechanism of this resistance is not fully understood, it is believed to operate at the level of virus replication rather than the immune response. It has been hypothesized that enhanced production of viral defective interfering (DI) particles is responsible for a substantial reduction in the titres of infectious virus in resistant mice. However, this has never been established at the molecular level since such particles have not been isolated and characterized. We have studied the products of virus replication in the brains of flavivirus-susceptible C3H/HeJ () and -resistant congenic C3H/RV () mice after an intracerebral challenge (i.c.) with Murray Valley encephalitis (MVE) virus and have found no evidence for the accumulation of truncated viral RNA in the brains of resistant mice. All three major viral RNA species, the replicative intermediate (RI), replicative form (RF) and virion RNA (vRNA) together with a subgenomic RNA species of 0·6 kb, which has not been previously described, were present in the brains of both mouse strains. However, the viral RF and RI RNA forms preferentially accumulated in the brains of resistant mice. Thus, we confirm that the resistance allele interferes with discrete steps in flavivirus replication, although the precise mechanism remains to be determined.

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1997-01-01
2022-05-23
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References

  1. Ausubel F. M., Brent R., Kingston R. E., Moore D. D., Smith J. A., Seidman J. G., Struhl K. 1988; Analysis of RNA by Northern hybridization. Current Protocols in Molecular Biology pp 4.9.1–4.9.8 Chichester: John Wiley & Sons;
    [Google Scholar]
  2. Bartholomeusz A. I., Wright P. J. 1993; Synthesis of dengue virus RNA in vitro : initiation and the involvement of proteins NS3 and NS5. Archives of Virology 128:111–121
    [Google Scholar]
  3. Brinton M. A. 1983; Analysis of extracellular West Nile virus particles produced by cell cultures from genetically resistant and susceptible mice indicates enhanced amplification of defective interfering particles by resistant cultures. Journal of Virology 46:860–870
    [Google Scholar]
  4. Chu P. W. G., Westaway E. G. 1985; Replication strategy of Kunjin virus: evidence for recycling role of replicative form RNA as template in semiconservative and asymmetric replication. Virology 140:68–79
    [Google Scholar]
  5. Chu P. W. G., Westaway E. G. 1987; Characterization of Kunjin virus RNA-dependent RNA polymerase: reinitiation of synthesis in vitro. Virology 157:330–337
    [Google Scholar]
  6. Cleaves G. R., Ryan T. E., Schlesinger R. W. 1981; Identification and characterization of type 2 dengue virus replicative intermediate and replicative form RNAs. Virology 111:73–83
    [Google Scholar]
  7. Dalgarno L., Trent D. W., Strauss J. H., Rice C. M. 1986; Partial nucleotide sequence of the Murray Valley encephalitis virus genome. Journal of Molecular Biology 187:309–323
    [Google Scholar]
  8. Darnell M. B., Koprowski H. 1974; Genetically determined resistance to infection with group B arboviruses. II. Increased production of interfering particles in cell cultures from resistant mice. Journal of Infectious Diseases 129:248–256
    [Google Scholar]
  9. Goodman G. T., Koprowski H. 1962; Study of the mechanism of innate resistance to virus infection. Journal of Cellular and Comparative Physiology 59:333–373
    [Google Scholar]
  10. Green M. C. 1989; Catalog of mutant genes and polymorphic loci. In Genetic Variants and Strains ofthe Laboratory Mouse pp 12–403 Green M. C. Edited by Stuttgart: Gustav Fischer;
    [Google Scholar]
  11. Groschel D., Koprowski H. 1965; Development of a virus-resistant inbred mouse strain for the study of innate resistance to arbo B viruses. Archiv fur die gesamte Virusforschung 17:379–391
    [Google Scholar]
  12. Grun J. B., Brinton M. A. 1986; Characterization of West Nile virus RNA-dependent RNA polymerase and cellular terminal adenylyl and uridylyl transferases in cell-free extracts. Journal of Virology 60:1113–1124
    [Google Scholar]
  13. Jacoby R. O., Bhatt P. N. 1976; Genetic resistance to lethal flavivirus encephalitis. I. Infection of congenic mice with Banzi virus. Journal of Infectious Disease 134:158–165
    [Google Scholar]
  14. Lee E., Fernon C., Simpson R., Weir R. C., Rice C. M., Dalgarno L. 1990; Sequence of the 3ʹ half of the Murray Valley encephalitis virus genome and mapping of the nonstructural proteins NS1, NS3 and NS5. Virus Genes 4:197–213
    [Google Scholar]
  15. Maniatis T., Fritsch E. F., Sambrook J. 1982 Molecular Cloning: A Laboratory Manual pp 150–162 Cold Spring Harbor, NY: Cold Spring Harbor Laboratory;
    [Google Scholar]
  16. Sabin A. B. 1952; Genetic, hormonal and age factors in natural resistance to certain viruses. Annals of the New York Academy of Sciences 54:936–944
    [Google Scholar]
  17. Sangster M. Y., Heliams D. B., Mackenzie J. S., Shellam G. R. 1993; Genetic studies of flavivirus resistance in inbred strains derived from wild mice : evidence for a new resistance allele at the flavivirus resistance locus (Flv). Journal of Virology 67:340–347
    [Google Scholar]
  18. Sangster M. Y., Urosevic N., Mansfield J. P., Mackenzie J. S., Shellam G. R. 1994; Mapping the Flv locus controlling resistance to flaviviruses on mouse chromosome 5. Journal of Virology 68:448–452
    [Google Scholar]
  19. Smith A. L., Jacoby R. O., Bhatt P. N. 1980; Genetic resistance to lethal flavivirus infection: detection of interfering virus produced in vivo. In Genetic Control of Natural Resistance to Infection and Malignancy pp 305–311 Skamene E., Kongshavn P., Landy M. Edited by New York: Academic Press;
    [Google Scholar]
  20. Urosevic N., Mansfield J. P., Mackenzie J. S., Shellam G. R. 1995; Low resolution mapping around the flavivirus resistance locus (Flv) on mouse chromosome 5. Mammalian Genome 6:454–458
    [Google Scholar]
  21. Wengler G., Wengler G., Gross H. J. 1978; Studies on virus-specific nucleic acids synthesized in vertebrate and mosquito cells infected with flaviviruses. Virology 89:423–437
    [Google Scholar]
  22. Wengler G., Bradley D. W., Collett M. S., Heinz F. X., Schlesinger R. W., Strauss J. H. 1994; Flaviviridae. In Virus Taxonomy Sixth Report ofthe International Committee on Taxonomy of Viruses pp 415–427 Murphy F. A., Fauquet C. M., Bishop D. H. L., Ghabrial S. A., Jarvis A. W., Martelli G. P., Mayo M. A., Summers M. D. Edited by Vienna & New York: Springer-Verlag;
    [Google Scholar]
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