Defective Interfering Particles of Fixed Rabies Viruses: Lack of Correlation with Attenuation or Auto-interference in Mice

Clark, H Fred; Parks, Nancy; Wunner, William H.

doi:10.1099/0022-1317-52-2-245

Cited by 29 publications

(16 citation statements)

References 32 publications

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“…Little is known about the role of DI viruses during natural infections although it has been pointed out that they have the capacity to ameliorate virulent infection or cause infections to become persistent (Huang & Baltimore, 1970;Dimmock, 1985;Barrett & Dimmock, 1986). In vivo laboratory infections with vesicular stomatitis virus (VSV) Holland & Villarreal, 1975;Rabinowitz et al, 1977;Crick & Brown, 1977;Fultz et al, 1981Fultz et al, , 1982a, rabies virus (Wiktor et al, 1977;Clark et al, 1981), reovirus (Spandidos & Graham, 1976), influenza virus (Bernkopf, 1950;yon Magnus, 1951 ;Gamboa et al, 1976;Rabinowitz & Huprikar, 1979), lymphocytic choriomeningitis virus (Welsh et al, 1977), Banzi virus (Smith, 1981), and Rift Valley fever virus (Mires, 1956) show that DI viruses do indeed exert a sparing effect, but it is uncertain that this is due to the interfering activity of the DI virus as no 'inactive' virus was used to control for stimulation of immune responses by DI virus antigen. Nonetheless, carefully controlled experiments using inactivated viral antigen in place of DI virus with VSV (Jones & Holland, 1980;Fultz et al, 1982 a) and Semliki Forest virus (SFV) (Dimmock & Kennedy, 1978;Crouch et al, 1982;Barrett & Dimmock, 1984a, b; showed that DI viruses are indeed powerful modulators of infection.…”

Section: Introductionmentioning

confidence: 99%

Protection of Mice from Lethal Influenza: Evidence that Defective Interfering Virus Modulates the Immune Response and Not Virus Multiplication

Dimmock¹,

Beck

McLain

1986

Journal of General Virology

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SUMMARYIntranasal administration of defective interfering (DI) influenza virus (A/WSN) ensured the survival of 80 ~ of C3H mice otherwise lethally infected with WSN by the intranasal route, whereas a control group which received fl-propiolactone-inactivated DI virus in place of DI virus died at 7.4 days post-infection. DI virus-treated mice developed significantly less lung consolidation than controls although qualitatively the cellular pathology in the two groups was indistinguishable. Surprisingly, in view of the accepted mode of action of DI virus interference, multiplication of infectious virus in the lung, production of viral haemagglutinin (HA) antigen and neuraminidase, and the distribution and amount of viral antigen in cells as shown by immune labelling were unaffected by the presence of active DI virus. Furthermore, assays of lung extracts showed that DI virus was not stimulating significantly greater amounts of interferon than the control inactivated DI virus. An alternative explanation arises from the fact that the pathology of influenza in inbred mice is immune (T lymphocyte)-mediated. Thus, since there is no evidence that DI virus affects virus multiplication we suggest that DI virus is responsible for ameliorating the damaging host responses. Another aspect of the immune response modulated by DI virus was the enhancement of local haemagglutination-inhibiting (HI) antibody in the lung, with peak increases of up to 10-fold over the relevant controls being demonstrated at 5 days after infection. This antibody was presumably complexed to HA antigen in the lung as activity was only demonstrated after elution at low pH. It had no detectable neutralizing activity (< 10 HI : neutralization ratio of convalescent serum) which accounts for the coexistence of local antibody and virus infectivity. Mice infected with virus alone or which received flpropiolactone-inactivated DI virus in addition to a lethal dose of WSN did not develop significant amounts of lung antibody. No differences were seen in serum HI titres. The increased level of antibody could not be attributed to the presence of greater amounts of HA antigen in lungs of mice treated with DI virus, as ELISA showed no significant difference from control preparations. The possibility that the two modulated immune responses are linked through HI antibody blocking access of T cells to cell membraneborne HA antigen is discussed.

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Section: Introductionmentioning

confidence: 99%

Protection of Mice from Lethal Influenza: Evidence that Defective Interfering Virus Modulates the Immune Response and Not Virus Multiplication

Dimmock¹,

Beck

McLain

1986

Journal of General Virology

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“…Fixed rabies virus strains differ greatly in their lethality for adult mice, and the factors governing the regulation of rabies virus pathogenicity appear to be diverse and variable, depending on virus growth conditions and virus strain (1)(2)(3)(4). In other virus systems, the virion structural proteins have been identified as determinants in pathogenicity.…”

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confidence: 99%

Characterization of an antigenic determinant of the glycoprotein that correlates with pathogenicity of rabies virus.

Dietzschold¹,

Wunner²,

Wiktor³

et al. 1983

Proc. Natl. Acad. Sci. U.S.A.

416

258

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The pathogenicity offixed rabies virus strains for adult mice depends on the presence of an antigenic determinant on the viral glycoprotein. Two virus-neutralizing monoclonal antibodies have been used to identify this determinant. All pathogenic strains of fixed rabies virus bind to these antibodies and are neutralized by them, whereas nonpathogenic strains fail to react with these monoclonal antibodies and are not neutralized by them. Antigenic variants of the rabies virus with altered glycoprotein were selected by growing virus in the presence of one monoclonal antibody, 194-2. All variants that lost their ability to react with this antibody and an additional antibody, 248-8, were found to be nonpathogenic for adult mice. Analysis of tryptic peptides of the glycoproteins of pathogenic parent virus and nonpathogenic 'variants and the amino acid sequence of a specific variant tryptic peptide revealed that the change in pathogenicity corresponded to an amino acid substitution at position 333 of the glycoprotein molecule. The nucleotide sequence of the nonpathogenic variant glycoprotein gene contained a base change that confirmed the single amino acid substitution in the tryptic peptide replacing arginine-333 in the parental glycoprotein. We conclude that arginine-333 is essential for the integrity of an antigenic determinant and for the ability of rabies viruses to produce lethal infection in adult mice.

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“…DI VSV preparations of defined particle length show differences in their abilities to induce the synthesis of interferon (Marcus & Sekellick, 1977), modulate infection in mice (Jones & Holland, 1980) and to autointerfere (Rao & Huang, 1982). Similarly, the in vivo properties of rabies virus in mice are variable (Clark et al, 1981). However, as yet there has been no systematic study of the biological activities of DI viruses in any system.…”

Section: Introductionmentioning

confidence: 99%

Defective Interfering Semliki Forest Virus Populations Are Biologically and Physically Heterogeneous

Barrett

Crouch

Dimmock

1984

Journal of General Virology

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SUMMARYThis study demonstrates that populations of defective interfering Semliki Forest virus (DI SFV) are heterogeneous particularly in respect of their interference properties. Interference was quantified by two assays, one measuring inhibition of the yield of infectious progeny virus, and the other measuring reduction in virus-directed RNA synthesis; for 11 different DI SFV preparations a ratio of the two interference titres was calculated. These ratios varied up to 46-fold indicating that each DI virus preparation contained an interference activity that varied independently of the other. However, sister stocks made from the same parental inoculum had similar properties. The effects of different DI virus preparations on other parameters (virus polypeptide synthesis, yield of DI virus and yield of infectious virus) were investigated using inocula with interference titres standardized by either assay. Co-inoculation of L929 cells with 50 p.f.u. SFV showed that these parameters varied independently of each other and of the DI virus inoculum. There was no correlation with the number of undiluted passages each DI stock had received. Direct evidence of physical heterogeneity was demonstrated by metrizamide density gradient centrifugation. Although infecting virus sedimented as a narrow band, DI SFV was distributed over a broad region of the gradient. Its position on the gradient indicated that DI SFV has a higher nucleic acid : protein ratio than standard virus. DI virus progeny obtained by using fractions of the gradient as inoculum were as heterogeneous as the unfractionated parent, confirming that DI viruses retain heterogeneity on passage.

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Defective Interfering Particles of Fixed Rabies Viruses: Lack of Correlation with Attenuation or Auto-interference in Mice

Cited by 29 publications

References 32 publications

Protection of Mice from Lethal Influenza: Evidence that Defective Interfering Virus Modulates the Immune Response and Not Virus Multiplication

Protection of Mice from Lethal Influenza: Evidence that Defective Interfering Virus Modulates the Immune Response and Not Virus Multiplication

Characterization of an antigenic determinant of the glycoprotein that correlates with pathogenicity of rabies virus.

Defective Interfering Semliki Forest Virus Populations Are Biologically and Physically Heterogeneous

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