Glycoprotein gE-negative Pseudorabies Virus has a Reduced Capability to Infect Second- and third-order Neurons of the Olfactory and Trigeminal Routes in the Porcine Central Nervous System

Mulder, W.A.; Jacobs, Liesbeth; Priem, J.; Kok, G. L.; Wagenaar, F.; Kimman, Tjeerd G.; Pol, J.M.A.

doi:10.1099/0022-1317-75-11-3095

Cited by 71 publications

(62 citation statements)

References 14 publications

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“…the olfactory, trigeminal, sympathetic and parasympathetic pathways (Babic et al, 1996). These results confirm and extend observations from other laboratories that PrV or HSV-1 gE is implicated in transneuronal transfer rather than in penetration and multiplication in first order neurons (Card et aL, 1992;Ba[an et aI., 1994;Kritas et al, 1994, Mulder et a]., 1994Dingwell et al, 1995;Standish et al, 1994).…”

Section: Introductionsupporting

confidence: 80%

Glycoprotein gH of Pseudorabies Virus is Essential for Penetration and Propagation in Cell Culture and in the Nervous System of Mice

Babic

Klupp

Makoschey

et al. 1996

Journal of General Virology

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Glycoprotein H (gH) of pseudorabies virus (PrV)is a structural component of the virion and forms a complex with another glycoprotein, gL. For a detailed analysis of the function of PrV gH, we isolated a gH-deficient mutant on transcomplementing gH-expressing cells after insertion of a p-galactosidase expression cassette into a partially deleted gH gene. The absence of gH did not affect primary or secondary attachment of PrV but the mutant was not infectious. The defect in infectivity could partially be overcome by experimentally induced membrane fusion using PEG, which suggests that gH was necessary for fusion between virion and cellular membranes. After intranasal inoculation into mice, the LDso of complemented gH PrV was more than four orders of magnitude higher than that of wild-type PrV. Infection of the respiratory epithelium was much less efficient with complemented gH PrV as compared with rescued PrV, reflecting the lack of direct cell-to-cell spread. Complemented gH PrV was able to penetrate into a few trigeminal and sympathetic first order neurons accessible from the nasal cavity, whereas transneuronal transfer in the second order neurons was not observed. In summary, gH is essential for entry and cell-to-cell spread in cell culture, and for propagation in the nervous system of mice. This substantiates the hypothesis that transneuronal spread in vivo and direct cell-to-cell spread in cell culture are governed by similar mechanisms.

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Section: Introductionsupporting

confidence: 80%

Glycoprotein gH of Pseudorabies Virus is Essential for Penetration and Propagation in Cell Culture and in the Nervous System of Mice

Babic

Klupp

Makoschey

et al. 1996

Journal of General Virology

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“…The glycoprotein E homologues are probably the best-analyzed envelope glycoproteins with an effect on viral neuroinvasion. Deletion of gE from the PrV genome has been shown to decrease virulence for pigs (28) by a block in infection of secondary neurons (20,21,30). Replication in the nasal mucosa and infection of primary neurons by gE-deleted virus strains probably is not or only slightly affected by deletion of gE (16,20,21).…”

Section: Discussionmentioning

confidence: 99%

“…Neuroinvasion of PrV occurs by ascending within the axon via anterograde and retrograde transport (2,4,6,20,21,30). Innervation of the nasal mucosa is provided by the olfactory and trigeminal nerves.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, the nervus trigeminus with all of its branches converges in the trigeminal ganglion leading to the pons and the brain stem. Therefore, after primary replication in the nasal mucosa, these two routes repre-sent the major ways of viral neuroinvasion toward the CNS (20,21,30), and the olfactory bulb and the sensory ganglia are major sites of latent virus (40).…”

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confidence: 99%

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Pseudorabies Virus Expressing Bovine Herpesvirus 1 Glycoprotein B Exhibits Altered Neurotropism and Increased Neurovirulence

Gerdts¹,

Beyer

Lomniczi

et al. 2000

J Virol

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Herpesvirus glycoproteins play dominant roles in the initiation of infection of target cells in culture and thus may also influence viral tropism in vivo. Whereas the relative contribution of several nonessential glycoproteins to neurovirulence and neurotropism of Pseudorabies virus (PrV), an alphaherpesvirus which causes Aujeszky's disease in pigs, has recently been uncovered in studies using viral deletion mutants, the importance of essential glycoproteins is more difficult to assess. We isolated an infectious PrV mutant, PrV-9112C2, which lacks the gene encoding the essential PrV glycoprotein B (gB) but stably carries in its genome and expresses the homologous gene of bovine herpesvirus 1 (BHV-1) (A. Kopp and T. C. Mettenleiter, J. Virol. 66:2754-2762, 1992). Apart from exhibiting a slight delay in penetration kinetics, PrV-9112C2 was similar in its growth characteristics in cell culture to wild-type PrV. To analyze the effect of the exchange of these homologous glycoproteins in PrV's natural host, swine, 4-week-old piglets were intranasally infected with 10 6 PFU of either wild-type PrV strain Kaplan (PrV-Ka), PrV-9112C2, or PrV-9112C2R, in which the PrV gB gene was reinserted instead of the BHV-1 gB gene. Animals infected with PrV-Ka and PrV-9112C2R showed a similar course of disease, i.e., high fever, marked respiratory symptoms but minimal neurological disorders, and excretion of high amounts of virus. All animals survived the infection. In contrast, animals infected with PrV-9112C2 showed no respiratory symptoms and developed only mild fever. However, on day 5 after infection, all piglets developed severe central nervous system (CNS) symptoms leading to death within 48 to 72 h. Detailed histological analyses showed that PrV-9112C2R infected all regions of the nasal mucosa and subsequently spread to the CNS preferentially by the trigeminal route. In contrast, PrV-9112C2 primarily infected the olfactory epithelium and spread via the olfactory route. In the CNS, more viral antigen and significantly more pronounced histological changes resulting in more severe encephalitis were found after PrV-9112C2 infection. Thus, our results demonstrate that replacement of PrV gB by the homologous BHV-1 glycoprotein resulted in a dramatic increase in neurovirulence combined with an alteration in the route of neuroinvasion, indicating that the essential gB is involved in determining neurotropism and neurovirulence of PrV.Pseudorabies virus (PrV) and Bovine herpesvirus 1 (BHV-1) are related alphaherpesviruses of the genus Varicellovirus. PrV, also designated Suid herpesvirus 1, is the causative agent of Aujeszky's disease (AD), a serious illness in domestic and wild animals. PrV has a broad host range and productively infects birds and most mammals, except for horses and higher primates including humans, which are resistant to infection (reviewed in reference 25). Whereas mortality in most infected species regularly amounts to 100%, pigs can survive a productive infection and remain latently infected for life. Thus, pigs a...

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“…For example, after intranasal inoculation in pigs, PRV gE deletion mutants had a reduced capability to propagate in olfactory and trigeminal pathways [56,79] and showed a reduced virulence in pigs [23,42,47,48]. A PRV vaccine carrying deletions in both gE and TK was shown to be innocuous but still highly immunogenic for pigs [72,120].…”

Section: ) Non-essential Glycoprotein Genesmentioning

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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Glycoprotein gE-negative Pseudorabies Virus has a Reduced Capability to Infect Second- and third-order Neurons of the Olfactory and Trigeminal Routes in the Porcine Central Nervous System

Cited by 71 publications

References 14 publications

Glycoprotein gH of Pseudorabies Virus is Essential for Penetration and Propagation in Cell Culture and in the Nervous System of Mice

Glycoprotein gH of Pseudorabies Virus is Essential for Penetration and Propagation in Cell Culture and in the Nervous System of Mice

Pseudorabies Virus Expressing Bovine Herpesvirus 1 Glycoprotein B Exhibits Altered Neurotropism and Increased Neurovirulence

Recombinant Viral Vector Vaccines for the Veterinary Use.

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