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The shape of pleomorphic virions determines resistance to cell-entry pressure | Nature Microbiology
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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. Filamentous viruses overcome antibody neutralization and inhibition of virus–cell membrane fusion more readily than spherical viruses.
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nature portfolio journals permissions reprints nature portfolio privacy policy advertising environmental pressures edward /tivanovic/ivanovic-lab-analysis-codes nature microbiology social media author information authors scientific advisory board middle author correspondence integrum scientific influenza-virus membrane fusion viral glycoprotein-dependent manner morphology-dependent entry kinetics nature+ nature 157 nature 371 nature 477 nature 376 nature 454 nature sample kolmogorov-smirnov tests springerlink instant access particle fluorescence-intensity quantification partially genetically encoded electron tomography reveals cell-death data plotted singlet-cell population analyzed particle-length distributions derived complete hc19-concentration dataset low-fidelity assembly permissions extended data fig triggering membrane fusion source data fig influenza viruses pseudotyped virus-specific epitopes influenza hemagglutinin structure m-fab inhibition panel influenza virus pseudotyped 7 single-particle measurements single-particle kinetics statistical source data article li ebola virus glycoprotein induce membrane merger tijana ivanovic
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headline:The shape of pleomorphic virions determines resistance to cell-entry pressure
description: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. Filamentous viruses overcome antibody neutralization and inhibition of virusâcell membrane fusion more readily than spherical viruses.
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