Viral Pathogens and ImmunityMutations Affecting the UL21 Gene Contribute to Avirulence of Pseudorabies Virus Vaccine Strain Bartha

Klupp, Barbara G.; Lomniczi, B.; Visser, Nico; Fuchs, Walter; Mettenleiter, Thomas C.

doi:10.1006/viro.1995.1504

Cited by 69 publications

(77 citation statements)

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“…The isogenic strains PRV-91 (gE-null), PRV-98 (gI-null), and PRV-160 (U S 9-null) (deletions of the gE, gI, and U S 9 genes, respectively) were previously described (4, 7, 30) (referenced in Table 1). The genome of the attenuated vaccine strain PRV-Bartha encodes a number of mutations, including deletion of a region of the unique short (U S ) region of the PRV genome, including the genes encoding U S 9, gE, gI, and U S 2 (described in detail elsewhere [3,14,16,18,19,22]). Two additional virulent strains, PRV-Kaplan and PRV-NIA3, used for these studies have been described elsewhere (13).…”

Section: Methodsmentioning

confidence: 99%

“…The genome of PRV-Bartha contains point mutations in the genes encoding gC, U L 21 and gM, as well as a deletion of several kilobase pairs in the U S region. The deletion in the U S region of the Bartha genome removes the coding sequences for U S 9 protein, as well as gE, gI, and U S 2 proteins (3,14,16,18,19,22). To determine the relative contributions of these genes to virulence in our studies, we infected mice with Becker isogenic strains, PRV-160 (U S 9-null), PRV-91 (gE-null), and PRV-98 (gI-null), which carry deletions in the genes encoding U S 9, gE, and gI, respectively.…”

Section: Distinctive Symptoms Of Virulent Prv Flank Infectionmentioning

confidence: 99%

“…Spread of infection of wild-type virus in the anterograde direction (from presynaptic to postsynaptic neurons) requires the PRV U S 9, gE, and gI proteins (4, 12). These genes are deleted in the PRV-Bartha strain (3,14,16,18,19,22). The U S 9, gE, and gI gene products are not required for spread in the retrograde direction.…”

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Two Modes of Pseudorabies Virus Neuroinvasion and Lethality in Mice

Brittle

Reynolds

Enquist

2004

J Virol

118

142

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We describe two distinct modes of neuroinvasion and lethality after murine flank inoculation with virulent and attenuated strains of pseudorabies virus (PRV). Mice infected with virulent (e.g., PRV-Becker, PRVKaplan, or PRV-NIA3) strains self-mutilate their flank skin in response to virally induced pruritus, die rapidly with no identifiable symptoms of central nervous system (CNS) infection such as behavioral abnormalities, and have little infectious virus or viral antigen in the brain. In distinct contrast, animals infected with an attenuated PRV vaccine strain (PRV-Bartha) survive approximately three times longer than wild-type PRVinfected animals, exhibit severe CNS abnormalities, and have an abundance of infectious virus in the brain at the time of death. Interestingly, these animals have no skin lesions and do not appear pruritic at any time during infection. The severe pruritus and relatively earlier time until death induced by wild-type PRV infection may reflect the peripheral nervous system (PNS) and immune responses to infection rather than a fatal, virally induced CNS pathology. Based on previously characterized afferent (sensory) and efferent (motor) neuronal pathways that innervate the skin, we deduced that wild-type virulent strains transit through the PNS via both afferent and efferent routes, whereas PRV-Bartha travels by only efferent routes in the PNS en route to the brain.Pseudorabies virus (PRV), a swine alphaherpesvirus, is a member of the alphaherpesvirus subfamily, including human and animal pathogens such as varicella-zoster virus, herpes simplex virus type 1 (HSV-1) and HSV-2, bovine herpesvirus types 1 and 5, and equine herpesviruses types 1 and 4 (23). Although the natural hosts of PRV are adult swine, PRV is pantropic, infecting avian embryos and a wide range of mammalian species, with the notable exceptions of humans and other higher-order species of nonhuman primates.PRV routinely establishes a latent infection in PNS ganglia of adult swine and yet rarely invades the central nervous systems (CNS) of these animals (8). Viral spread between adult swine occurs primarily via direct mucosal contact. Common sequelae of wild-type PRV infection include respiratory disease, weight loss, and infertility in pregnant gilts and sows (31). In contrast, PRV infection is lethal in neonatal piglets and in nonnative hosts such as cows, dogs, rodents, and other susceptible animals. In these animals, infection induces severe, uncontrollable pruritus (itchiness), culminating in frantic selfmutilating behavior historically described as "mad itch." Death ensues within days of infection with virulent strains of PRV. The cause of death of these animals has traditionally been ascribed to fatal encephalitis.Adult swine infected with live, attenuated vaccine strains such as PRV-Bartha typically exhibit few, if any, symptoms of infection. In addition, most attenuated PRV strains are significantly less virulent in nonnative hosts such as rodents (8). Despite the attenuated phenotype, PRV-Bartha remains neuroinvas...

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Section: Methodsmentioning

confidence: 99%

Section: Distinctive Symptoms Of Virulent Prv Flank Infectionmentioning

confidence: 99%

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Two Modes of Pseudorabies Virus Neuroinvasion and Lethality in Mice

Brittle

Reynolds

Enquist

2004

J Virol

118

142

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“…It also carries mutations within the gC gene which include an alteration in the aminoterminal signal sequence resulting in inefficient intracellular translocation and incorporation of this protein into the viral envelope [82]. Lastly, point mutations within the UL21 gene, whose product is involved in capsid formation, contribute to the avirulence of PrV Bartha [52]. Restoration of all three defects is required for recovery of the virulent phenotype.…”

Section: Attenuationmentioning

confidence: 99%

Aujeszky's disease (pseudorabies) virus: the virus and molecular pathogenesis - State of the art, June 1999

2000

Self Cite

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-Considerable progress has been made during the last years in understanding the molecular basis of protein function in pseudorabies virus (PrV), the causative agent of Aujeszky's disease (AD). Major topics have been the identification and functional characterisation of viral envelope glycoproteins and cellular virus receptors, elucidation of viral proteins involved in neurovirulence and neuropathogenesis, detection and characterisation of attenuating mutations present in and leading to successful attenuated live vaccines, and the near completion of the genomic sequence of PrV DNA. This review, which follows an article prepared for the 1993 AD symposium in Budapest, Hungary, will briefly summarise those recent developments and update the reader on the current state of the art in PrV research. Aujeszky's disease / pseudorabies virus / glycoprotein / molecular pathogenesis / tropismRésumé -Le virus de la maladie d'Aujeszky : virus et pathogenèse au niveau moléculaire -État des lieux, Juin 1999. Ces dernières années ont donné lieu à des progrès considérables pour la compréhension des bases moléculaires de la fonction des protéines du virus de la maladie d'Aujeszky (VMA). Les principaux sujets d'étude ont été l'identification et la caractérisation fonctionnelle des glycoprotéines d'enveloppe et des récepteurs cellulaires pour le virus, la mise en évidence des protéines virales impliquées dans la neurovirulence et la neuropathogenèse, la détection et la caractéri-sation de mutations atténuantes présentes et pouvant conduire à des vaccins atténués efficaces, et l'achèvement presque total de la séquence génomique de l'ADN du virus. Cette revue de la littéra-ture, qui fait suite à un article préparé pour le symposium de Budapest, Hongrie, sur la maladie d'Aujeszky (1993), va résumer ces développements récents, et faire une mise à jour, pour le lecteur, des recherches menées dans ce domaine. maladie d'Aujeszky / pseudorabies virus / glycoprotéine / pathogenèse moléculaire Vet. Res. 31 (2000) 99-115 99

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“…Deletion of the UL21 gene leads to a striking attenuation of PrV without markedly impairing immunogenicity (Klupp et al, 1995).…”

Section: The Alphaherpesvirus Pseudorabies Virus (Prv) Causesmentioning

confidence: 99%

Deletion of glycoprotein gM of pseudorabies virus results in attenuation for the natural host.

Dijkstra

Gerdts

Klupp

et al. 1997

Journal of General Virology

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Glycoprotein M (gM) is one of the very few nonessential glycoproteins conserved throughout the herpesvirus family. Despite this conservation little is known about its function in virus replication. To test for the importance of gM in vivo in a natural virus-host system, 6-week-old piglets were intranasally infected with a gM N mutant of the alphaherpesvirus pseudorabies virus (PrV). Following infection virus excretion from the nasal mucosa was decreased ca. 100-fold compared to wild-type or revertant virus. Clinical signs were limited to transiently elevated temperature. In contrast, animals infected by wild-type or revertant virus exhibited high fever, severe respiratory symptoms and affliction of the central nervous system. Prior infection with gM N PrV conferred protection against challenge infection and animals mounted an antibody response against gM after wild-type virus infection. Thus, gM is important for efficient virus replication in vivo and deletion of gM may contribute to development of live attenuated, genetically marked vaccines.

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Viral Pathogens and ImmunityMutations Affecting the UL21 Gene Contribute to Avirulence of Pseudorabies Virus Vaccine Strain Bartha

Cited by 69 publications

References 0 publications

Two Modes of Pseudorabies Virus Neuroinvasion and Lethality in Mice

Two Modes of Pseudorabies Virus Neuroinvasion and Lethality in Mice

Aujeszky's disease (pseudorabies) virus: the virus and molecular pathogenesis - State of the art, June 1999

Deletion of glycoprotein gM of pseudorabies virus results in attenuation for the natural host.

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