The shape of pleomorphic virions determines resistance to cell-entry pressure
Many enveloped animal viruses produce a variety of particle shapes, ranging from small spherical to long filamentous types. Characterization of how the shape of the virion affects infectivity has been difficult because the shape is only partially genetically encoded, and most pleomorphic virus structures have no selective advantage in vitro. Here, we apply virus fractionation using low-force sedimentation, as well as antibody neutralization coupled with RNAScope, single-particle membrane fusion experiments and stochastic simulations to evaluate the effects of differently shaped influenza A viruses and influenza viruses pseudotyped with Ebola glycoprotein on the infection of cells. Our results reveal that the shape of the virus particles determines the probability of both virus attachment and membrane fusion when viral glycoprotein activity is compromised. The larger contact interface between a cell and a larger particle offers a greater probability that several active glycoproteins are adjacent to each other and can cooperate to induce membrane merger. Particles with a length of tens of micrometres can fuse even when 95% of the glycoproteins are inactivated. We hypothesize that non-genetically encoded variable particle shapes enable pleomorphic viruses to overcome selective pressure and may enable adaptation to infection of cells by emerging viruses such as Ebola. Our results suggest that therapeutics targeting filamentous virus particles could overcome antiviral drug resistance and immune evasion in pleomorphic viruses.
| Errataetall: |
CommentIn: Nat Microbiol. 2021 May;6(5):536-537. - PMID 33927384 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:6 |
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| Enthalten in: |
Nature microbiology - 6(2021), 5 vom: 18. Mai, Seite 617-629 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Li, Tian [VerfasserIn] |
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| Links: |
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Journal Article |
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| Anmerkungen: |
Date Completed 31.08.2021 Date Revised 19.04.2022 published: Print-Electronic CommentIn: Nat Microbiol. 2021 May;6(5):536-537. - PMID 33927384 Citation Status MEDLINE |
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| doi: |
10.1038/s41564-021-00877-0 |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Many enveloped animal viruses produce a variety of particle shapes, ranging from small spherical to long filamentous types. Characterization of how the shape of the virion affects infectivity has been difficult because the shape is only partially genetically encoded, and most pleomorphic virus structures have no selective advantage in vitro. Here, we apply virus fractionation using low-force sedimentation, as well as antibody neutralization coupled with RNAScope, single-particle membrane fusion experiments and stochastic simulations to evaluate the effects of differently shaped influenza A viruses and influenza viruses pseudotyped with Ebola glycoprotein on the infection of cells. Our results reveal that the shape of the virus particles determines the probability of both virus attachment and membrane fusion when viral glycoprotein activity is compromised. The larger contact interface between a cell and a larger particle offers a greater probability that several active glycoproteins are adjacent to each other and can cooperate to induce membrane merger. Particles with a length of tens of micrometres can fuse even when 95% of the glycoproteins are inactivated. We hypothesize that non-genetically encoded variable particle shapes enable pleomorphic viruses to overcome selective pressure and may enable adaptation to infection of cells by emerging viruses such as Ebola. Our results suggest that therapeutics targeting filamentous virus particles could overcome antiviral drug resistance and immune evasion in pleomorphic viruses | ||
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| 700 | 1 | |a Li, Zhenyu |e verfasserin |4 aut | |
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| 700 | 1 | |a Liu, Meisui |e verfasserin |4 aut | |
| 700 | 1 | |a Chandran, Kartik |e verfasserin |4 aut | |
| 700 | 1 | |a Ivanovic, Tijana |e verfasserin |4 aut | |
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