Profiling of Glycan Receptors for Minute Virus of Mice in Permissive Cell Lines Towards Understanding the Mechanism of Cell Recognition

Halder, Sujata; Cotmore, Susan F.; Heimburg-Molinaro, Jamie; Smith, David F.; Cummings, Richard D.; Chen, Xi; Trollope, Alana; North, Simon J.; Haslam, Stuart M.; Dell, Anne; Tattersall, Peter; McKenna, Robert; Agbandje‐McKenna, Mavis

doi:10.1371/journal.pone.0086909

Cited by 16 publications

(14 citation statements)

References 56 publications

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“…While the MGAT1 - CHO cell line was similarly sensitive to the MVMp strain as wild type CHO-S cells, it was resistant to MVMc infection (Table 2). The receptor protein for MVM have not yet been identified, but it has been demonstrated that MVMp binds to sialic acid residues from both N and O linked glycosylation (55–57). Knocking out MGAT1 does not alter the O-linked glycosylation pathway, perhaps explaining why the line remains sensitive to MVMp.…”

Section: Resultsmentioning

confidence: 99%

CRISPR/Cas9 gene editing for the creation of an MGAT1 deficient CHO cell line to control HIV-1 vaccine glycosylation

Byrne

O’Rourke

Alexánder

et al. 2018

Preprint

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Over the last decade multiple broadly neutralizing monoclonal antibodies (bN-mAbs) to the HIV-1 envelope protein, gp120, have been described. Surprisingly many of these recognize epitopes consisting of both amino acid and glycan residues. Moreover, the glycans required for binding of these bN-mAbs are early intermediates in the N-linked glycosylation pathway. This type of glycosylation substantially alters the mass and net charge of HIV envelope (Env) proteins compared to molecules with the same amino acid sequence but possessing mature, complex (sialic acid containing) carbohydrates. Since cell lines suitable for biopharmaceutical production that limit N-linked glycosylation to mannose-5 (Man5) or earlier intermediates are not readily available, the production of vaccine immunogens displaying these glycan dependent epitopes has been challenging. Here we report the development of a stable suspension adapted CHO cell line that limits glycosylation to Man5 and earlier intermediates. This cell line was created using the CRISPR/Cas9 gene editing system and contains a mutation that inactivates the gene encoding Mannosyl (Alpha-1,3-)-Glycoprotein Beta-1,2-N-Acetylglucosaminyltransferase (MGAT1). Monomeric gp120s produced in the MGAT1- CHO cell line exhibit improved binding to prototypic glycan dependent bN-mAbs directed to the V1/V2 domain (e.g. PG9) and the V3 stem (e.g. PGT128 and 10–1074) while preserving the structure of the important glycan independent epitopes (e.g. VRC01). The ability of the MGAT1-CHO cell line to limit glycosylation to early intermediates in the N-linked glycosylation pathway, without impairing the doubling time or ability to grow at high cell densities, suggest that it will be a useful substrate for the biopharmaceutical production of HIV-1 vaccine immunogens.

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Section: Resultsmentioning

confidence: 99%

CRISPR/Cas9 gene editing for the creation of an MGAT1 deficient CHO cell line to control HIV-1 vaccine glycosylation

Byrne

O’Rourke

Alexánder

et al. 2018

Preprint

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“…For other members, for example H-1 Parvovirus (H-1PV), LuIII, MVM, and Porcine Parvovirus (PPV), SIA binding is essential for infection and the recognition is to N-acetyl neuraminic acid. MVM utilizes terminal SIA on an unknown glycoprotein for cellular recognition [4] and binds specifically to α2-3 N-linked sialylated glycans including the s(Le x ) 3 motif [81,82]. This Lewis X motif is over expressed in cancer cells and likely dictates MVM's oncotropism [83].…”

Section: Glycans Receptor Utilization By the Autonomous Parvoviruses mentioning

confidence: 99%

Parvovirus glycan interactions

Huang

Halder

Agbandje‐McKenna

2014

Current Opinion in Virology

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108

102

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Members of the Parvoviridae utilize glycan receptors for cellular attachment and subsequent interactions determine transduction efficiency or pathogenic outcome. This review focuses on the identity of the glycan receptors utilized, their capsid binding footprints, and a discussion of the overlap of these sites with tropism, transduction, and pathogenicity determinants. Despite high sequence diversity between the different genera, most parvoviruses bind to negatively charged glycans, such as sialic acid and heparan sulfate, abundant on cell surface membranes. The capsid structure of these viruses exhibit high structural homology enabling common regions to be utilized for glycan binding and at the same time the sequence diversity at the common footprints allows for binding of different glycans or differential binding of the same glycan.

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“…For instance, the Feline and Canine parvoviruses, belonging to the genus Protoparvovirus , require the transferrin receptor for the entry process [ 26 ]. Regarding the Rodent protoparvovirus species, sialic acid has been identified as an important mediator for cell membrane recognition and entry for the MVM and H-1PV viruses [ 27 - 29 ], though the cognate cell receptors remain to be identified.…”

Section: Introductionmentioning

confidence: 99%

Oncolytic parvoviruses: from basic virology to clinical applications

Marchini

Bonifati

Scott

et al. 2015

Virol J

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Accumulated evidence gathered over recent decades demonstrated that some members of the Parvoviridae family, in particular the rodent protoparvoviruses H-1PV, the minute virus of mice and LuIII have natural anticancer activity while being nonpathogenic to humans. These studies have laid the foundations for the launch of a first phase I/IIa clinical trial, in which the rat H-1 parvovirus is presently undergoing evaluation for its safety and first signs of efficacy in patients with glioblastoma multiforme. After a brief overview of the biology of parvoviruses, this review focuses on the studies which unraveled the antineoplastic properties of these agents and supported their clinical use as anticancer therapeutics. Furthermore, the development of novel parvovirus-based anticancer strategies with enhanced specificity and efficacy is discussed, in particular the development of second and third generation vectors and the combination of parvoviruses with other anticancer agents. Lastly, we address the key challenges that remain towards a more rational and efficient use of oncolytic parvoviruses in clinical settings, and discuss how a better understanding of the virus life-cycle and of the cellular factors involved in virus infection, replication and cytotoxicity may promote the further development of parvovirus-based anticancer therapies, open new prospects for treatment and hopefully improve clinical outcome.

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Profiling of Glycan Receptors for Minute Virus of Mice in Permissive Cell Lines Towards Understanding the Mechanism of Cell Recognition

Cited by 16 publications

References 56 publications

CRISPR/Cas9 gene editing for the creation of an MGAT1 deficient CHO cell line to control HIV-1 vaccine glycosylation

CRISPR/Cas9 gene editing for the creation of an MGAT1 deficient CHO cell line to control HIV-1 vaccine glycosylation

Parvovirus glycan interactions

Oncolytic parvoviruses: from basic virology to clinical applications

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