Pseudorabies virus glycoproteins gII and gp50 are essential for virus penetration

Rauh, Isabella; Mettenleiter, Thomas C.

doi:10.1128/jvi.65.10.5348-5356.1991

Cited by 190 publications

(120 citation statements)

References 43 publications

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“…Initially, we examined the subcellular distribution of the viral glycoprotein gB in neurons that were infected with wild-type, gEnull, and Us9-null viruses. gB is an abundant viral membrane protein that is required for virus entry and cell-to-cell spread in all cells (Rauh and Mettenleiter, 1991). The kinetics of expression and the cellular localization of gB were indistinguishable in the cell body of neurons infected with all three viruses ( Fig.…”

Section: Resultsmentioning

confidence: 94%

A conservedα-herpesvirus protein necessary for axonal localization of viral membrane proteins

Tomishima

Enquist

2001

The Journal of Cell Biology

116

151

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Pseudorabies virus, an α-herpesvirus, is capable of infecting the nervous system and spreading between synaptically connected neurons in diverse hosts. At least three viral membrane proteins (gE, gI, and Us9) are necessary for the spread of infection from presynaptic to postsynaptic neurons (anterograde spread) in infected rodents. To understand how these proteins effect anterograde spread between neurons, we analyzed the subcellular localization of viral proteins after infection of cultured rat sympathetic neurons with wild-type or mutant viruses. After Us9-null mutant infections but not gE-null mutant infections, only a subset of the viral structural proteins had entered axons. Surprisingly, capsid and tegument proteins but not viral membrane proteins were detected in axons. The spread of Us9 missense mutants in the rodent nervous system correlated with the amount of viral membrane proteins localized to axons. We conclude that the Us9 membrane protein controls axonal localization of diverse viral membrane proteins but not that of capsid or tegument proteins. The data support a model where virion subassemblies but not complete virions are transported in the axon. Our results provide new insight into the process of virion assembly and exit from neurons that leads to directional spread of herpesviruses in the nervous system.

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Section: Resultsmentioning

confidence: 94%

A conservedα-herpesvirus protein necessary for axonal localization of viral membrane proteins

Tomishima

Enquist

2001

The Journal of Cell Biology

116

151

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“…Glycoprotein B is a critical factor in herpesvirus infections. Since numerous reports have described gB as the virus entry mediator for example, [52][53][54][55][56], the main goal of our study was to provide new data on the roles of alphaherpesvirus gB expressed in the cells, which should correspond to the situation in of the post-entry phases of infection, i.e., when it appears as a product of an early-late gene [57][58][59]. We could address its localization in the endosomal and lysosomal compartments, including CD63-and MHC II-positive structures, its targeting to EVs and its immunomodulatory effect on the cellular MHC II.…”

Section: Discussionmentioning

confidence: 99%

Alphaherpesvirus gB Homologs Are Targeted to Extracellular Vesicles, but They Differentially Affect MHC Class II Molecules

Grabowska

Wąchalska

Graul

et al. 2020

Viruses

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Herpesvirus envelope glycoprotein B (gB) is one of the best-documented extracellular vesicle (EVs)-incorporated viral proteins. Regarding the sequence and structure conservation between gB homologs, we asked whether bovine herpesvirus-1 (BoHV-1) and pseudorabies virus (PRV)-encoded gB share the property of herpes simplex-1 (HSV-1) gB to be trafficked to EVs and affect major histocompatibility complex (MHC) class II. Our data highlight some conserved and differential features of the three gBs. We demonstrate that mature, fully processed BoHV-1 and PRV gBs localize to EVs isolated from constructed stable cell lines and EVs-enriched fractions from virus-infected cells. gB also shares the ability to co-localize with CD63 and MHC II in late endosomes. However, we report here a differential effect of the HSV-1, BoHV-1, and PRV glycoprotein on the surface MHC II levels, and MHC II loading to EVs in stable cell lines, which may result from their adverse ability to bind HLA-DR, with PRV gB being the most divergent. BoHV-1 and HSV-1 gB could retard HLA-DR exports to the plasma membrane. Our results confirm that the differential effect of gB on MHC II may require various mechanisms, either dependent on its complex formation or on inducing general alterations to the vesicular transport. EVs from virus-infected cells also contained other viral glycoproteins, like gD or gE, and they were enriched in MHC II. As shown for BoHV-1 gB-or BoHV-1-infected cell-derived vesicles, those EVs could bind anti-virus antibodies in ELISA, which supports the immunoregulatory potential of alphaherpesvirus gB.

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“…Vero cells expressing wild-type gH or the gDH hybrid protein have been published (3,19). Construction of mutant viruses lacking gB or gH followed standard procedures (3,12,37). Insertion of a green fluorescent protein expression cassette facilitated the isolation of virus mutants.…”

Section: Methodsmentioning

confidence: 99%

“…Besides gD, gB and the gH-gL complex are required for penetration of free virions into target cells (reviewed in references 27 and 42). However, in contrast to the situations in herpes simplex virus type 1 (HSV-1) and bovine herpesvirus type 1 (BHV-1), PrV gD is dispensable for direct viral cell-to-cell spread in vitro (9,23,32,37). Thus, phenotypically complemented gD-negative PrV (PrV-gD Ϫ ) is able to infect primary target cells and subsequently spreads via direct cell-to-cell transmission.…”

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confidence: 99%

Glycoprotein D-Independent Infectivity of Pseudorabies Virus Results in an Alteration of In Vivo Host Range and Correlates with Mutations in Glycoproteins B and H

Schmidt¹,

Gerdts²,

Beyer

et al. 2001

J Virol

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Pass is replication competent with an only moderate reduction in specific infectivity but appears to bind to receptors different from those recognized by wild-type PrV (A. Karger, J. Schmidt, and T. C. Mettenleiter, J. Virol. 72:7341-7348, 1998). To analyze whether this alteration in receptor usage in vitro influences infection in vivo, the model host mouse and the natural host pig were intranasally infected with PrV-gD ؊ Pass and were compared to animals infected by wild-type PrV. For mice, a comparable progress of disease was observed, and all animals infected with mutant virus died, although they exhibited a slight delay in the onset of symptoms and, correspondingly, a longer time to death. In contrast, whereas wild-type PrV-infected pigs showed clinical signs and histological and histopathological findings typical of PrV infection, no signs of disease were observed after infection with PrV-gD ؊ Pass. Moreover, in these animals, virus-infected cells were not detectable by immunohistochemical staining of different organ samples and no virus could be isolated from nasal swabs. Mutations in glycoproteins B and H were found to correlate with, and probably contribute to, gD-independent infectivity. In conclusion, although PrV-gD ؊ Pass is virulent in mice, it is apparently unable to infect the natural host, the pig. This altered host range in vivo correlates with a difference of receptor usage in vitro and demonstrates for the first time the importance of gD receptors in alphaherpesvirus infection of an animal host.

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Pseudorabies virus glycoproteins gII and gp50 are essential for virus penetration

Cited by 190 publications

References 43 publications

A conservedα-herpesvirus protein necessary for axonal localization of viral membrane proteins

A conservedα-herpesvirus protein necessary for axonal localization of viral membrane proteins

Alphaherpesvirus gB Homologs Are Targeted to Extracellular Vesicles, but They Differentially Affect MHC Class II Molecules

Glycoprotein D-Independent Infectivity of Pseudorabies Virus Results in an Alteration of In Vivo Host Range and Correlates with Mutations in Glycoproteins B and H

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