Non-transmissible pseudorabies virus gp50 mutants: a new generation of safe live vaccines

Peeters, Ben; Bouma, A.; Bruin, Tiny de; Moormann, R.J.M.; Gielkens, A. L. J.; Kimman, Tjeerd G.

doi:10.1016/0264-410x(94)90104-x

Cited by 25 publications

(21 citation statements)

References 29 publications

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“…The role of the four essential mediators of fusion may also differ in entry of free virus and cell-cell spread. Pseudorabies virus requires gD for entry of free virus but not for cell-cell spread (30,31,37), and antibodies against HSV-1 gL can block syncytium formation without affecting the entry of free virus (29). Finally, although wild-type bovine herpesvirus 1, like HSV, requires gD for entry of free virus and cell-cell spread, a point mutation in the bovine herpesvirus gH ectodomain is sufficient to restore to a gD-null virus the capability for cell-cell spread but not the ability to enter as free virus (45,46).…”

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Mutations in Herpes Simplex Virus Glycoprotein D Distinguish Entry of Free Virus from Cell-Cell Spread

Rauch

Rodríguez

Roller

2000

J Virol

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Herpes simplex virus type 1 (HSV-1) glycoprotein D (gD) is an essential component of the entry apparatus that is responsible for viral penetration and subsequent cell-cell spread. To test the hypothesis that gD may serve distinguishable functions in entry of free virus and cell-cell spread, mutants were selected for growth on U S 11cl19.3 cells, which are resistant to both processes due to the lack of a functional gD receptor, and then tested for their ability to enter as free virus and to spread from cell to cell. Unlike their wild-type parent, HSV-1(F), the variants that emerged from this selection, which were named SP mutants, are all capable of forming macroscopic plaques on the resistant cells. This ability is caused by a marked increase in cell-cell spread without a concomitant increase in efficiency of entry of free virus. gD substitutions that arose within these mutants are sufficient to mediate cell-cell spread in U S 11cl19.3 cells but are insufficient to overcome the restriction to entry of free virions. These results suggest that mutations in gD (i) are sufficient but not necessary to overcome the block to cell-cell spread exhibited by U S 11cl19.3 cells and (ii) are insufficient to mediate entry of free virus in the same cells.Herpes simplex virus (HSV) can enter a naive host cell by either of two distinct methods. Extracellular virions present during primary infection can enter cells in exposed tissue by entry of free virus. Once a cell is initially infected, subsequent infections can begin by lateral spread from the initially infected cell to adjacent uninfected neighbors by cell-cell spread. Both types of entry are important for sustained viral infection. The ability of a virus to spread from cell to cell provides a powerful advantage in vivo since it is able to avoid the strong humoral immune response elicited to extracellular HSV virions. The essential roles of HSV glycoproteins in entry of free virus and cell-cell spread remain poorly characterized.HSV entry requires a complicated cascade of virus-cell interactions. Initially, an interaction between cellular heparan sulfate proteoglycan and viral glycoprotein C (gC) and/or gB results in attachment of the virion to the cell surface (15,16,20,47,56). Fusion between the viral membrane and the cellular plasma membrane is not triggered until a secondary interaction occurs between gD and a cellular receptor (12,17,21,54). The fusion event itself requires the coordinated function of the viral glycoproteins gB, gD, gH, and gL. These four proteins play essential roles in both entry of free virus and cell-cell spread (3,11,43). These two processes are thus closely related. However, entry of free virus and cell-cell spread can be distinguished in HSV and in related alphaherpesviruses by their differing dependence on specific viral genes and by their differing sensitivities to mutations in the viral genome. Deletion of the viral glycoproteins gE and gI provides a clear distinction between entry of free virus and cell-cell spread since it significantly red...

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confidence: 99%

Mutations in Herpes Simplex Virus Glycoprotein D Distinguish Entry of Free Virus from Cell-Cell Spread

Rauch

Rodríguez

Roller

2000

J Virol

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“…When cells or animals are inoculated with phenotypically complemented PRV gD mutants, the virus is able to spread by means of direct cell-to-cell transmission, but progeny virions released by infected cells are non-infectious (Peeters et al, 1993 ;Heffner et al, 1993). Furthermore, it has been shown that PRV gD mutants can be used as a vaccine to protect pigs against Aujeszky's disease (Heffner et al, 1993 ;Peeters et al, 1994Peeters et al, , 1995Mettenleiter et al, 1994). This finding suggests that PRV gD mutants may also be used as biologically safe, non-transmissible vaccine vectors for the expression of antigens of unrelated viruses.…”

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confidence: 76%

“…Furthermore, as indicated previously (Peeters et al, 1995), transfer of genes present in the gD locus to PRV field strains by means of homologous recombination results in replacement of the gD gene, yielding non-infectious recombinants. In several experiments, we (Peeters et al, 1994) and others (Heffner et al, 1993) were unable to detect infectious virus in animals inoculated with PRV gD mutants. The emergence of variants with gDindependent infectivity as observed in cell culture by Schmidt et al (1997) is highly unlikely in vivo since the virus completes only a limited number of cell passages and eventually will be cleared from the inoculated animal by immunological mechanisms.…”

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Biologically safe, non-transmissible pseudorabies virus vector vaccine protects pigs against both Aujeszky's disease and classical swine fever.

Peeters¹,

Bieńkowska-Szewczyk²,

Hulst³

et al. 1997

Journal of General Virology

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Envelope glycoprotein D (gD) of pseudorabies virus (PRV) is essential for penetration but is not required for cell-to-cell spread. When animals are inoculated with a phenotypically complemented PRV gD mutant, the virus is able to spread locally by means of direct cell-to-cell transmission, but progeny virions released by infected cells are non-infectious because they lack gD. Therefore, the virus cannot be transmitted from inoculated animals to other animals. This property makes a PRV gD mutant an attractive candidate as a safe vaccine vector. To examine whether a self-restricted, non-transmissible PRV mutant can be used as a biologically safe vaccine vector, a gD/gE-negative PRV recombinant virus which expresses envelope glycoprotein E2 of classical swine fever virus was constructed. Vaccination of pigs showed that the recombinant virus was able to protect pigs against both Aujeszky's disease and classical swine fever.

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“…One way to overcome both of these concerns is to construct a vaccine which has only limited capacity for replication. Peeters et al [87] described a replication defective vaccine based on PRV. The gD of PRV is essential for virus entry but is not required for subsequent steps in virus replication cycle.…”

Section: ) Essential Glycoprotein D Genementioning

confidence: 99%

Recombinant Viral Vector Vaccines for the Veterinary Use.

Yokoyama

Maeda

Mikami

1997

The Journal of Veterinary Medical Science

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ABSTRACT. Recently, genetically engineering using recombinant DNA techniques has been applied to design new viral vaccines in order to reduce some problems which present viral vaccines have. Up to now, many viruses have been investigated for development of recombinant attenuated vaccines or live viral vectors for delivery of foreign immunogenic antigens. In this review, we introduced three kind of viruses; herpesviruses, vaccinia viruses, and adenoviruses, which have best widely been studied as recombinant vaccines or delivery vaccines for the veterinary use. -KEY WORDS: recombinant polyvalent vaccine, recombinant vaccine, viral vector.

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Non-transmissible pseudorabies virus gp50 mutants: a new generation of safe live vaccines

Cited by 25 publications

References 29 publications

Mutations in Herpes Simplex Virus Glycoprotein D Distinguish Entry of Free Virus from Cell-Cell Spread

Mutations in Herpes Simplex Virus Glycoprotein D Distinguish Entry of Free Virus from Cell-Cell Spread

Biologically safe, non-transmissible pseudorabies virus vector vaccine protects pigs against both Aujeszky's disease and classical swine fever.

Recombinant Viral Vector Vaccines for the Veterinary Use.

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