Contributions of the Four Essential Entry Glycoproteins to HSV-1 Tropism and the Selection of Entry Routes
In: mBio, Jg. 12 (2021-04-01), Heft 2
Online
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Zugriff:
Herpes simplex viruses (HSV-1 and HSV-2) contain up to 16 different proteins in their envelopes. Four of these, glycoproteins gB, gD, gH, and gL, are termed essential with regard to entry, whereas the rest are typically referred to as nonessential based on the entry phenotypes of the respective single genetic deletions.
Herpes simplex viruses (HSV-1 and HSV-2) encode up to 16 envelope proteins, four of which are essential for entry. However, whether these four proteins alone are sufficient to dictate the broad cellular tropism of HSV-1 and the selection of different cell type-dependent entry routes is unknown. To begin addressing this, we previously pseudotyped vesicular stomatitis virus (VSV), lacking its native glycoprotein G, with only the four essential entry glycoproteins of HSV-1: gB, gH, gL, and gD. This novel VSVΔG-BHLD pseudotype recapitulated several important features of HSV-1 entry: the requirement for gB, gH, gL, gD, and a cellular receptor and sensitivity to anti-gB and anti-gH/gL neutralizing antibodies. However, due to the use of a single cell type in that study, the tropism of the VSVΔG-BHLD pseudotype was not investigated. Here, we show that the cellular tropism of the pseudotype is severely limited compared to that of wild-type HSV-1 and that its entry pathways differ from the native HSV-1 entry pathways. To test the hypothesis that other HSV-1 envelope proteins may contribute to HSV-1 tropism, we generated a derivative pseudotype containing the HSV-1 glycoprotein C (VSVΔG-BHLD-gC) and observed a gC-dependent increase in entry efficiency in two cell types. We propose that the pseudotyping platform developed here has the potential to uncover functional contributions of HSV-1 envelope proteins to entry in a gain-of-function manner.
Titel: |
Contributions of the Four Essential Entry Glycoproteins to HSV-1 Tropism and the Selection of Entry Routes
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Autor/in / Beteiligte Person: | Hilterbrand, Adam T. ; Daly, Raecliffe ; Heldwein, Ekaterina E. |
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Zeitschrift: | mBio, Jg. 12 (2021-04-01), Heft 2 |
Veröffentlichung: | American Society for Microbiology, 2021 |
Medientyp: | unknown |
ISSN: | 2150-7511 (print) |
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