Cleavage of the bovine herpesvirus glycoprotein B is not essential for its function

Blewett, Earl L.; Misra, Vikram

doi:10.1099/0022-1317-72-9-2083

Cited by 16 publications

(11 citation statements)

References 46 publications

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“…Given the unimpaired exposure of gB at the cell surface of this artefactual transformant it can be concluded that proteolytic cleavage of gB is not a prerequisite for its natural transport. This view is in agreement with data reported for bovine herpesvirus (Blewett & Misra, 1991). In the context of transport of gB to the cell surface it is noteworthy that in transformed cell lines an increasing number of multinucleated cells was found upon prolonged culturing (unpublished observation), an observation which may imply a function for gB in membrane fusion.…”

Section: Discussionsupporting

confidence: 81%

Stable constitutive expression of glycoprotein B (gpUL55) of human cytomegalovirus in permissive astrocytoma cells

Reis

Bogner

Reschke

et al. 1993

Journal of General Virology

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Section: Discussionsupporting

confidence: 81%

Stable constitutive expression of glycoprotein B (gpUL55) of human cytomegalovirus in permissive astrocytoma cells

Reis

Bogner

Reschke

et al. 1993

Journal of General Virology

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“…In addition to those studies, it has been proposed that residues 477 to 510 of BHV-1 gB (equivalent to residues 485 to 518 of HSV-2 gB) form a heptad repeat, and a synthetic peptide corresponding to this region interfered with virus spread but not with penetration (25). For HCMV gB and BHV-1 gB, mutagenesis of the highly basic proteolytic cleavage site that is found in some but not all gB homologs showed that cleavage is not essential for protein function (2,37).…”

Section: Fig 2 Quantitation Of Virus Entry (Complementation)mentioning

confidence: 99%

Identification of Functional Domains in Herpes Simplex Virus 2 Glycoprotein B

Minova-Foster

Norton

et al. 2006

J Virol

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Glycoprotein B (gB) is one of four membrane proteins that are essential for the entry of herpes simplex viruses (HSV) into cells, and coexpression of the same combination of proteins in transfected cells results in cell fusion. The latter effect is reminiscent of the ability of virus infection to cause cell fusion, particularly since the degree of fusion is greatly increased by syncytial mutations in gB. Despite intensive efforts with the gB homologs of HSV and some other herpesviruses, information about functionally important regions in the 700-amino-acid ectodomain of this protein is very limited at present. This is largely due to the misfolding of the majority of the mutants examined. It was shown previously that the percentage of correctly folded mutants could be increased by targeting only predicted loop regions (i.e., not alpha-helix or beta-strand), and by using this approach new functional domains in HSV-2 gB have now been identified.Glycoprotein B (gB) is conserved throughout the Herpesviridae family and seems likely to have a function in membrane fusion for each virus, although significant details may vary and some homologs may have additional functions such as attachment. The gB homologs of herpes simplex virus 1 (HSV-1) and HSV-2, which share an 87% sequence identity, are essential for entry of the viruses into cells and for cell-to-cell spread (4,6,8,19,33). Nevertheless, much remains to be learned about regions of these proteins that are important for their functional activity. One approach to this problem was to characterize HSV-1 mutants resistant to neutralization by complement-independent anti-gB monoclonal antibodies (MAbs). This identified a small number of altered residues within the corresponding epitopes (14, 17), which are likely to be in a functionally important region of the protein. The mutations fall within a region comprising amino acids 273 to 298 (where the signal peptide is not included in the numbering), corresponding to amino acids 276 to 301 of HSV-2 gB. Another approach was targeted substitution of residues in the region adjacent to the transmembrane anchor; of those which could be mutated without disrupting protein folding, two (G716 and G736, equivalent to G721 and G741 of HSV-2 gB, excluding the signal sequence) were found to be important for virus entry (40). For some other HSV glycoproteins, such as gC, gD, and gH, functional domains have been mapped by linker-insertion mutagenesis, in which short oligonucleotides are ligated into restriction sites within the gene (7,12,15,35). This method has had only limited success with gB due to misfolding of the majority of the mutants (5,24,29).Combining experimental data with a secondary structure prediction made by the PHD neural network method (32), based on a multiple sequence alignment of 19 alphaherpesvirus gB sequences, it was shown previously that no mutants with insertions in predicted ␣-helices or ␤-strands folded correctly (24). In contrast, 50% of mutants with insertions in predicted loops, rather than ␣-helices or ␤-str...

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“…In contrast to many other viral proteins involved in membrane fusion (White, 1990;Spear, 1987), failure to cleave gB homologues has no effect on their function in penetration or cell-cell fusion (Blewett & Misra, 1991;Pereira, 1994), although spread of infection from cell to cell can be retarded (Kopp et al, 1994). However, oligomerization of the gB homologues may play a role in the infectious process since the formation ofhomodimers ofHSV-1 gB, which is not cleaved, appears to be required for infectivity of HSV-1 (Pereira, 1994).…”

Section: Effect Of Glycosylation On Cleavage Of Ehv-1 Gbmentioning

confidence: 99%

N-terminal sequence analysis of equine herpesvirus 1 glycoproteins D and B and evidence for internal cleavage of the gene 71 product

Wellington

Gooley

Love

et al. 1996

Journal of General Virology

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Signal cleavage sites of equine herpesvirus 1 (EHV-1) glycoproteins D and B (gD and gB) and an endoproteolytic cleavage site of EHV-1 gB were determined by N-terminal amino acid sequencing and compared with known cleavage sites of homologues in other herpesviruses. Signal cleavage of EHV-1 gD occurred between Arg 35 and Ala 36 in a region of basic amino acids resembling the endoproteolytic cleavage sites of viral glycoproteins, nine amino acids downstream of the predicted site, while EHV-1 gB was cleaved as predicted between Ala s5 and Val s~. Endoproteolytic cleavage of EHV-1 gB occurred between Arg 54s and Ala 5aa, 28 amino acids downstream of the cleavage site predicted from conserved sequences of other herpesvirus gB homologues. One interpretation of these data is that EHV-1 gB is cleaved internally at both sites, a possibility which was supported by the apparent molecular masses of the unglycosylated gB subunits produced in the presence of tunicamycin. This double cleavage would release a stretch of amino acids which is not present in sequenced gB molecules of other herpesviruses. Experiments with glycosylation inhibitors indicated that cleavage of EHV-1 gB can occur in the absence of glycosylation. N-terminal sequencing also determined that a 42 kDa EHV-1 glycoprotein was a product of internal cleavage of the protein encoded by gene 71. Staggered endoproteolytic cleavage after adjacent arginine residues 506 and 507 separates the 42 kDa Cterminal subunit containing all the cysteine residues from the serine and threonine rich N-terminal region.

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Cleavage of the bovine herpesvirus glycoprotein B is not essential for its function

Cited by 16 publications

References 46 publications

Stable constitutive expression of glycoprotein B (gpUL55) of human cytomegalovirus in permissive astrocytoma cells

Stable constitutive expression of glycoprotein B (gpUL55) of human cytomegalovirus in permissive astrocytoma cells

Identification of Functional Domains in Herpes Simplex Virus 2 Glycoprotein B

N-terminal sequence analysis of equine herpesvirus 1 glycoproteins D and B and evidence for internal cleavage of the gene 71 product

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