Addicted to sugar: roles of glycans in the order<i>Mononegavirales</i>

Ortega, Victoria; Stone, Jacquelyn A.; Contreras, Erik; Iorio, Ronald M.; Aguilar, Hector C.

doi:10.1093/glycob/cwy053

Cited by 15 publications

(19 citation statements)

References 253 publications

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“…4 A ). VSVG, a type I transmembrane protein that only undergoes N -glycosylation ( 32 ), served as a negative control. In cells expressing GFP-CD8a, TfR-GFP, or VSVG-SBP-GFP (in the presence of biotin), we observed that, whereas none appeared at the Golgi in control treatment, CD8a and TfR, but not VSVG, displayed strong Golgi localization under GalNAc- O -Bn treatment ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Glycans function as a Golgi export signal to promote the constitutive exocytic trafficking

Sun

Tie

Chen

et al. 2020

Journal of Biological Chemistry

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Most proteins in the secretory pathway are glycosylated. However, the role of glycans in membrane trafficking is still unclear. Here, we discovered that transmembrane secretory cargos, such as interleukin 2 receptor α subunit or Tac, transferrin receptor and cluster of differentiation 8a, unexpectedly displayed substantial Golgi localization when their O-glycosylation was compromised. By quantitatively measuring their Golgi residence times, we found that the observed Golgi localization of O-glycan deficient cargos is due to their slow Golgi export. Using a super-resolution microscopy method that we previously developed, we revealed that O-glycan deficient Tac chimeras localize at the interior of the trans-Golgi cisternae. O-glycans were observed to be both necessary and sufficient for the efficient Golgi export of Tac chimeras. By sequentially introducing O-glycosylation sites to ST6GAL1, we demonstrated that O-glycan’s effect on Golgi export is probably additive. Finally, the finding that N-glycosylated GFP substantially reduces the Golgi residence time of a Tac chimera suggests that N-glycans might have a similar effect. Therefore, both O- and N-glycans might function as a generic Golgi export signal at the trans-Golgi to promote the constitutive exocytic trafficking.

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Section: Resultsmentioning

confidence: 99%

Glycans function as a Golgi export signal to promote the constitutive exocytic trafficking

Sun

Tie

Chen

et al. 2020

Journal of Biological Chemistry

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“…Finally, a paradigm shift is also needed to advance the field of glycovirology. For example, a comprehensive survey of known glycosylation in Mononegavirales was recently published [57]. Had the authors known about ViralZone, the valuable though PDF-static information printed in this article could have been structured in a way to be stored straightaway in the database and enhance virus annotation.…”

Section: Discussionmentioning

confidence: 99%

A Bioinformatics View of Glycan–Virus Interactions

Mercier

Mariethoz

Lascano-Maillard

et al. 2019

Viruses

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Evidence of the mediation of glycan molecules in the interaction between viruses and their hosts is accumulating and is now partially reflected in several online databases. Bioinformatics provides convenient and efficient means of searching, visualizing, comparing, and sometimes predicting, interactions in numerous and diverse molecular biology applications related to the -omics fields. As viromics is gaining momentum, bioinformatics support is increasingly needed. We propose a survey of the current resources for searching, visualizing, comparing, and possibly predicting host–virus interactions that integrate the presence and role of glycans. To the best of our knowledge, we have mapped the specialized and general-purpose databases with the appropriate focus. With an illustration of their potential usage, we also discuss the strong and weak points of the current bioinformatics landscape in the context of understanding viral infection and the immune response to it.

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“…Journal of Virology which could significantly change charge distribution on the surface of VSV particles, possibly reducing the repulsion. These mutations could also reduce repulsion by posttranslational modifications of VSV-G: for example, VSV-G N-glycosylation that occurs through the N163 and N320 positions (85)(86)(87)(88)(89)(90)(91)(92). The VGV-G N-glycosylation can dramatically affect viral infectivity, although the effect strongly depends on the target cell type and specific mode of VSV-G N-glycosylation (89,90,93).…”

Section: Experimental Evolution Of Vsv In Cancer Cellsmentioning

confidence: 99%

“…These mutations could also reduce repulsion by posttranslational modifications of VSV-G: for example, VSV-G N-glycosylation that occurs through the N163 and N320 positions (85)(86)(87)(88)(89)(90)(91)(92). The VGV-G N-glycosylation can dramatically affect viral infectivity, although the effect strongly depends on the target cell type and specific mode of VSV-G N-glycosylation (89,90,93). Moreover, it is believed that one of the major mechanisms of DEAE-dextran-mediated improvement of VSV infection is removal of repulsion between negatively charged molecules on the cell surface (such as anionic phospholipid sialic acid residues) and terminal sialic acid residues associated with those N-glycosylated VSV-G (89).…”

Section: Experimental Evolution Of Vsv In Cancer Cellsmentioning

confidence: 99%

Experimental Evolution Generates Novel Oncolytic Vesicular Stomatitis Viruses with Improved Replication in Virus-Resistant Pancreatic Cancer Cells

Seegers

Frasier

Greene

et al. 2020

J Virol

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Vesicular stomatitis virus (VSV) based oncolytic viruses are promising agents against various cancers. We have shown that pancreatic ductal adenocarcinoma (PDAC) cell lines exhibit great diversity in susceptibility and permissibility to VSV. Here, using a directed evolution approach with our two previously described oncolytic VSV recombinants, VSV-p53wt and VSV-p53-CC, we generated novel oncolytic VSVs with an improved ability to replicate in virus-resistant PDAC cell lines. VSV-p53wt and VSV-p53-CC encode a VSV matrix protein (M) with a ΔM51 mutation (M-ΔM51) and one of two versions of a functional human tumor suppressor, p53, fused to a far-red fluorescent protein, eqFP650. Each virus was serially passaged 32 times (which accounts for more than 60 viral replication cycles) on either the SUIT-2 (moderately resistant to VSV) or MIA PaCa-2 (highly permissive to VSV) human PDAC cell lines. While no phenotypic changes were observed for MIA PaCa-2-passaged viruses, both SUIT-2-passaged VSV-p53wt and VSV-p53-CC showed improved replication in SUIT-2 and AsPC-1, another human PDAC cell line also moderately resistant to VSV, while remaining highly attenuated in nonmalignant cells. Surprisingly, two identical VSV glycoprotein (VSV-G) mutations, K174E and E238K, were identified in both SUIT-2-passaged viruses. Additional experiments indicated that the acquired G mutations improved VSV replication, at least in part due to improved virus attachment to SUIT-2 cells. Importantly, no mutations were found in the M-ΔM51 protein, and no deletions or mutations were found in the p53 or eqFP650 portions of virus-carried transgenes in any of the passaged viruses, demonstrating long-term genomic stability of complex VSV recombinants carrying large transgenes. IMPORTANCE Vesicular stomatitis virus (VSV)-based oncolytic viruses are promising agents against pancreatic ductal adenocarcinoma (PDAC). However, some PDAC cell lines are resistant to VSV. Here, using a directed viral evolution approach, we generated novel oncolytic VSVs with an improved ability to replicate in virus-resistant PDAC cell lines, while remaining highly attenuated in nonmalignant cells. Two independently evolved VSVs obtained 2 identical VSV glycoprotein mutations, K174E and E238K. Additional experiments indicated that these acquired G mutations improved VSV replication, at least in part due to improved virus attachment to SUIT-2 cells. Importantly, no deletions or mutations were found in the virus-carried transgenes in any of the passaged viruses. Our findings demonstrate long-term genomic stability of complex VSV recombinants carrying large transgenes and support further clinical development of oncolytic VSV recombinants as safe therapeutics for cancer.

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Addicted to sugar: roles of glycans in the orderMononegavirales

Cited by 15 publications

References 253 publications

Glycans function as a Golgi export signal to promote the constitutive exocytic trafficking

Glycans function as a Golgi export signal to promote the constitutive exocytic trafficking

A Bioinformatics View of Glycan–Virus Interactions

Experimental Evolution Generates Novel Oncolytic Vesicular Stomatitis Viruses with Improved Replication in Virus-Resistant Pancreatic Cancer Cells

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