Vaccinia virus: a suitable vehicle for recombinant vaccines?

Kaplan, C.

doi:10.1007/bf01311044

Cited by 43 publications

(24 citation statements)

References 39 publications

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“…Despite their apparent efficacy, a major concern about the use of live VV recombinants as vaccines lies in the potential for complications such as post-vaccinial encephalitis (Kaplan, 1989). Animal studies have therefore been carried out to compare the virulence of VV recombinants with that of the parental wild-type (wt) virus.…”

Section: Introductionmentioning

confidence: 99%

Comparison of the Virulence of Wild-type Thymidine Kinase (tk)-deficient and tk+ Phenotypes of Vaccinia Virus Recombinants after Intranasal Inoculation of Mice

Taylor¹,

Stott²,

Wertz

et al. 1991

Journal of General Virology

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A recombinant vaccinia virus vector was constructed which expressed the major surface glycoprotein G of human respiratory syncytial virus (RSV) and the thymidine kinase (tk) gene of vaccinia virus. The virulence of this tk ÷ recombinant virus was compared with that of a tk-recombinant and the wild-type (wt) virus after intranasal inoculation of mice. Respiratory infection with wt virus resulted in a lethal infection with widespread dissemination of virus. In contrast, infection with the tk-recombinant was not lethal and the virus had a reduced ability to disseminate to extrapulmonary tissue compared with wt virus. Insertion of the tk gene restored the virulence of the recombinant virus to the level of that of the wt virus. Despite a dramatic reduction in virulence of the tkrecombinant, virus could occasionally be recovered from the brains of mice. The expression of the attachment glycoprotein of RSV appeared to enhance the ability of the tk-recombinant virus to replicate in the lungs when compared with recombinants expressing fusion or nucleoprotein genes. The results confirm that inactivation of the tk gene results in a dramatic reduction of virulence for mice but suggest that there is still a potential danger of infection of the brain following intranasal administration of virus.

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Section: Introductionmentioning

confidence: 99%

Comparison of the Virulence of Wild-type Thymidine Kinase (tk)-deficient and tk+ Phenotypes of Vaccinia Virus Recombinants after Intranasal Inoculation of Mice

Taylor¹,

Stott²,

Wertz

et al. 1991

Journal of General Virology

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“…The WR strain of VACV is a mouse-adapted neurovirulence strain (20,28). The amino terminus of E3 is necessary for this phenotype in C57BL/6 mice, as the deletion of this domain results in the inability of the virus to replicate in the brain to titers comparable to those of wtVACV, and it has a 1,000-times-higher LD 50 (8).…”

Section: Pathogenesis Of Vacve3l⌬83n Is Restored To Wtvacv Levels In mentioning

confidence: 99%

The Amino Terminus of the Vaccinia Virus E3 Protein Is Necessary To Inhibit the Interferon Response

White

Jacobs

2012

J Virol

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Vaccinia virus (VACV) encodes a multifunctional protein, E3L, that is necessary for interferon (IFN) resistance in cells in culture. Interferon resistance has been mapped to the well-characterized carboxy terminus of E3L, which contains a conserved double-stranded RNA binding domain. The amino terminus of E3L has a Z-form nucleic acid binding domain, which has been shown to be dispensable for replication and IFN resistance in HeLa and RK13 cells; however, a virus expressing E3L deleted of the amino terminus has reduced pathogenicity in an animal model. In this study, we demonstrate that the pathogenicity of a virus expressing E3L deleted of the amino terminus was fully rescued in type I IFN receptor knockout (IFN-α/βR −/− ) mice. Furthermore, this virus was IFN sensitive in primary mouse embryo fibroblasts (MEFs). This virus induced the phosphorylation of the α subunit of eukaryotic initiation factor 2 (eIF2α) in MEFs in an IFN-dependent manner. The depletion of double-stranded RNA-dependent protein kinase (PKR) from these MEFs restored the IFN resistance of this virus. Furthermore, the virus expressing E3L deleted of the amino terminus was also IFN resistant in PKR −/− MEFs. Thus, our data demonstrate that the amino terminus of E3L is necessary to inhibit the type I IFN response both in mice and in MEFs and that in MEFs, the amino terminus of E3L functions to inhibit the PKR pathway.

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“…This is important, because the development of recombinant vaccinia viruses expressing foreign genes is in progress and may result in a new generation of live vaccines. But this also presents problems, because attenuated and genetically stable viruses are required (Edwards et al, 1988;Altenburger et al, 1989;Kaplan et al, 1989) and many of these recombinant virus strains are known to be 0000-9552 © 1990 SGM pathogenic to laboratory animals. On the other hand, the number of cases in which cowpox and cowpox-like strains cause localized skin lesions in man, pets and zoo animals is increasing (Mahnel, 1986;Bennett et al, 1989;Mahnel et al, 1989).…”

Section: Introductionmentioning

confidence: 99%

Structural and functional analysis of orthopoxvirus epitopes with neutralizing monoclonal antibodies

Czerny¹,

Mahnel²

1990

Journal of General Virology

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Vaccinia virus: a suitable vehicle for recombinant vaccines?

Cited by 43 publications

References 39 publications

Comparison of the Virulence of Wild-type Thymidine Kinase (tk)-deficient and tk+ Phenotypes of Vaccinia Virus Recombinants after Intranasal Inoculation of Mice

Comparison of the Virulence of Wild-type Thymidine Kinase (tk)-deficient and tk+ Phenotypes of Vaccinia Virus Recombinants after Intranasal Inoculation of Mice

The Amino Terminus of the Vaccinia Virus E3 Protein Is Necessary To Inhibit the Interferon Response

Structural and functional analysis of orthopoxvirus epitopes with neutralizing monoclonal antibodies

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