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Tytuł pozycji:

The shape of pleomorphic virions determines resistance to cell-entry pressure.

Tytuł:
The shape of pleomorphic virions determines resistance to cell-entry pressure.
Autorzy:
Li T; Biochemistry Department, Brandeis University, Waltham, MA, USA.
Li Z; Biochemistry Department, Brandeis University, Waltham, MA, USA.
Deans EE; Biochemistry Department, Brandeis University, Waltham, MA, USA.
Mittler E; Department of Microbiology and Immunology, Albert Einstein College of Medicine, New York, NY, USA.
Liu M; Biochemistry Department, Brandeis University, Waltham, MA, USA.
Chandran K; Department of Microbiology and Immunology, Albert Einstein College of Medicine, New York, NY, USA.
Ivanovic T; Biochemistry Department, Brandeis University, Waltham, MA, USA. .
Źródło:
Nature microbiology [Nat Microbiol] 2021 May; Vol. 6 (5), pp. 617-629. Date of Electronic Publication: 2021 Mar 18.
Typ publikacji:
Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.
Język:
English
Imprint Name(s):
Original Publication: [London] : Nature Publishing Group, [2016]-
MeSH Terms:
Virus Attachment*
Influenza A virus/*physiology
Influenza, Human/*virology
Viral Envelope Proteins/*chemistry
Virion/*physiology
Cell Line ; Humans ; Influenza A virus/chemistry ; Influenza A virus/ultrastructure ; Viral Envelope Proteins/metabolism ; Virion/chemistry ; Virion/ultrastructure
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Grant Information:
R01 AI134824 United States AI NIAID NIH HHS; DP2 GM128204 United States GM NIGMS NIH HHS
Substance Nomenclature:
0 (Viral Envelope Proteins)
Entry Date(s):
Date Created: 20210319 Date Completed: 20210831 Latest Revision: 20220419
Update Code:
20240105
DOI:
10.1038/s41564-021-00877-0
PMID:
33737748
Czasopismo naukowe
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.
Comment in: Nat Microbiol. 2021 May;6(5):536-537. (PMID: 33927384)

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