Characterization of Vesicular Stomatitis Virus Pseudotypes Bearing Essential Entry Glycoproteins gB, gD, gH, and gL of Herpes Simplex Virus 1

Rogalin, Henry B.; Heldwein, Ekaterina E.

doi:10.1128/jvi.01714-16

Cited by 22 publications

(32 citation statements)

References 59 publications

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“…As expected, HSV-1 entered all receptor-bearing cells but not receptor-negative B78H1 or CHO-K1 cells (Fig 2A). VSVΔG-BHLD pseudotype also readily infected C10 cells but not parent B78H1 cells (Fig 2B), consistent with previous observations (27). VSVΔG-BHLD pseudotype also infected CHO-HVEM and CHO-nectin-1 cells in a receptor-dependent manner albeit with much lower efficiency (Fig 2B).…”

Section: Resultssupporting

confidence: 92%

“…Previously, we showed that the VSVΔG-BHLD pseudotype efficiently entered C10 cells and that its entry recapitulated several important features of HSV-1 entry into susceptible cells: the requirement for gB, gH, gL, gD, and a gD receptor, and sensitivity to anti-gB and anti-gH/gL neutralizing antibodies (27). Here, we expanded this study to six additional HSV-1-susceptible cell lines and found that out of seven, only C10 and CHO-HVEM cells supported appreciable VSVΔG-BHLD entry.…”

Section: Discussionmentioning

confidence: 90%

“…To begin addressing this question, we previously generated VSV lacking its native glycoprotein G and pseudotyped with HSV-1 gB, gH, gL, and gD through trans -complementation, which we refer to as the VSVΔG-BHLD pseudotype (27). The VSVΔG-BHLD pseudotype efficiently entered C10 cells (B78 murine melanoma cells expressing nectin-1), and its entry recapitulated several important features of HSV-1 entry into susceptible cells, namely, the requirement for gB, gH, gL, gD, and a gD receptor, as well as sensitivity to anti-gB and anti-gH/gL neutralizing antibodies (27). However, this study left unclear whether the VSVΔG-BHLD pseudotype could enter any HSV-1 susceptible cell types or specify native entry routes.…”

Section: Introductionmentioning

confidence: 99%

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Contributions of the four essential entry glycoproteins to HSV-1 tropism and the selection of entry routes

Hilterbrand

Daly

Heldwein

2020

Preprint

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15Herpes Simplex viruses (HSV-1 and HSV-2) encode up to 15 glycosylated and unglycosylated 16 envelope proteins. Four of these, gB, gH, gL, and gD, are essential for entry and mediate cell-cell 17 fusion when co-expressed in uninfected, receptor-bearing cells. However, their contributions to 18 HSV-1 tropism and the selection of entry routes are unclear. To begin addressing this, we 19 previously pseudotyped VSV lacking its native glycoprotein, G, with HSV-1 glycoproteins gB, 20 gH, gL, and gD. This novel VSVDG-BHLD pseudotype recapitulated several aspects of HSV-1 21 entry: it could enter murine C10 cells, required gB, gH, gL, gD, and a cellular receptor for entry, 22 AUTHOR SUMMARY 37Different viruses enter cells by diverse routes, but how that choice is made is not always clear. 38Understanding the mechanisms behind these choices is vital for finding strategies to prevent viral 39 infections. In enveloped viruses, viral proteins embedded in the envelope accomplish this task. 40While most enveloped viruses encode one or two envelope proteins, Herpes Simplex viruses 41 (HSV) encode up to 15. Four of these are deemed essential for entry (gB, gH, gL, and gD) 42 whereas the rest have been termed non-essential. While these four proteins are essential, their 43 contributions to HSV-1 cellular tropism and entry pathways have not been fully elucidated. Here, 44we generated virions that have only the four essential HSV-1 glycoproteins on their surface. We 45show that the VSVDG-BHLD pseudotype has a narrower tropism than HSV-1 and uses different 46 entry pathways. Thus, the four essential HSV-1 entry glycoproteins alone do not define HSV-1 47 55All viruses must enter cells to initiate infection, and different viruses accomplish this task by 56 different mechanisms: some penetrate cells at the plasma membrane while others hijack host 57 endocytic pathways. Enveloped viruses -those in which the nucleocapsid is surrounded by a 58 cell-derived lipid bilayer -penetrate the cells by merging their lipid envelopes with a cellular 59 membrane, either the plasma membrane or the membrane of an endocytic vesicle following 60 endocytosis ( Fig 1) [reviewed in (1, 2)]. Viruses typically have preferred entry routes, the choice 61 of which is not always clear, and some enter different target cells by different routes. 62Understanding what routes viruses use to enter cells and how they select them may help inform 63 strategies to prevent viral infections. 64Herpes Simplex viruses (HSV-1 and HSV-2) are enveloped alphaherpesviruses that infect 65 much of the world's population for life, causing a panoply of diseases ranging from painful to 66 life-threatening (3, 4). An enduring mystery of HSV entry is how and why the virus enters 67 different cells by different routes: direct fusion with the plasma membrane [e.g., neurons, Vero 68 cells, Hep2 cells, reviewed in (5)] or by endocytosis and subsequent fusion with the endosomal 69 membrane [e.g., keratinocytes, corneal epithelial cells (6, 7)]. 70HSV-1 encodes 15 viral envelope proteins, ...

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Section: Resultssupporting

confidence: 92%

Section: Discussionmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

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Contributions of the four essential entry glycoproteins to HSV-1 tropism and the selection of entry routes

Hilterbrand

Daly

Heldwein

2020

Preprint

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“…We believe that these peptides may be interacting with glycoprotein D, which is the least conserved protein between both viruses (85%) and is responsible for the activation of the heterodimer gH-gL [42,51]. …”

Section: Discussionmentioning

confidence: 99%

“…For herpes simplex viruses, the viral entry process takes place with the aid of 4 viral glycoproteins: gD, gB, gH, and gL, all of which have been proven to be essential for these viruses to carry out membrane fusion [42]. …”

Section: Discussionmentioning

confidence: 99%

Peptides Derived from Glycoproteins H and B of Herpes Simplex Virus Type 1 and Herpes Simplex Virus Type 2 Are Capable of Blocking Herpetic Infection in vitro

Cetina-Corona¹,

López-Sánchez²,

Salinas-Trujano³

et al. 2016

Intervirology

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Aims: The aim of this study was to design peptides derived from glycoproteins H (gH) and B (gB) of herpes simplex viruses type 1 (HSV-1) and type 2 (HSV-2) with the potential to block herpetic infection and to evaluate their ability to inhibit HSV-1 and HSV-2 infection in vitro. Methods: A library of continuous 15-25 residue stretches (CRSs) located at the surface of gH and gB from HSV-1 and HSV-2 was created. These CRSs were analyzed, and only those that were highly flexible and rich in charged residues were selected for the design of the antiviral peptides (AVPs). The toxicity of the AVPs was evaluated by MTT reduction assays. Virucidal activity of the AVPs was determined by a plaque reduction assay, and their antiviral effect was measured by cell viability assays. Results and Conclusion: Four AVPs (CB-1, CB-2, U-1, and U-2) derived from gB and gH were designed and synthetized, none of which showed high levels of toxicity in Vero cells. The U-1 and U-2 gB-derived AVPs showed high virucidal and antiviral activities against both HSV-1 and HSV-2. The gH-derived peptide CB-1 showed high virucidal and antiviral activities against HSV-2, while CB-2 showed similar results against HSV-1. The peptides CB-1 and CB-2 showed higher IC₅₀ values than the U-1 and U-2 peptides.

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Expression, Purification, and Crystallization of HSV-1 Glycoproteins for Structure Determination

White¹,

Stampfer²,

Heldwein³

2019

Methods in Molecular Biology

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Characterization of Vesicular Stomatitis Virus Pseudotypes Bearing Essential Entry Glycoproteins gB, gD, gH, and gL of Herpes Simplex Virus 1

Cited by 22 publications

References 59 publications

Contributions of the four essential entry glycoproteins to HSV-1 tropism and the selection of entry routes

Contributions of the four essential entry glycoproteins to HSV-1 tropism and the selection of entry routes

Peptides Derived from Glycoproteins H and B of Herpes Simplex Virus Type 1 and Herpes Simplex Virus Type 2 Are Capable of Blocking Herpetic Infection in vitro

Expression, Purification, and Crystallization of HSV-1 Glycoproteins for Structure Determination

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