Atomic structure of a rhinovirus C, a virus species linked to severe childhood asthma

Yue Liu; Marchel G. Hill; Thomas Klose; Zhenguo Chen; Kelly Watters; Yury A. Bochkov; Wen Jiang; Ann C. Palmenberg; Michael G. Rossmann

doi:10.1073/pnas.1606595113

Atomic structure of a rhinovirus C, a virus species linked to severe childhood asthma

Yue Liu, Marchel G. Hill, Thomas Klose, Zhenguo Chen, Kelly Watters, Yury A. Bochkov, Wen Jiang, Ann C. Palmenberg, Michael G. Rossmann

Research output: Contribution to journal › Article › peer-review

55 Scopus citations

Abstract

Isolates of rhinovirus C (RV-C), a recently identified Enterovirus (EV) species, are the causative agents of severe respiratory infections among children and are linked to childhood asthma exacerbations. The RV-C have been refractory to structure determination because they are difficult to propagate in vitro. Here, we report the cryo-EM atomic structures of the full virion and native empty particle (NEP) of RV-C15a. The virus has 60 "fingers" on the virus outer surface that probably function as dominant immunogens. Because the NEPs also display these fingers, they may have utility as vaccine candidates. A sequence-conserved surface depression adjacent to each finger forms a likely binding site for the sialic acid on its receptor. The RV-C, unlike other EVs, are resistant to capsid-binding antiviral compounds because the hydrophobic pocket in VP1 is filled with multiple bulky residues. These results define potential molecular determinants for designing antiviral therapeutics and vaccines.

Original language	English (US)
Pages (from-to)	8997-9002
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	113
Issue number	32
DOIs	https://doi.org/10.1073/pnas.1606595113
State	Published - Aug 9 2016

Keywords

Rhinovirus c|cryoelectron microscopy|atomic structure|asthma

ASJC Scopus subject areas

General

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10.1073/pnas.1606595113

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title = "Atomic structure of a rhinovirus C, a virus species linked to severe childhood asthma",

abstract = "Isolates of rhinovirus C (RV-C), a recently identified Enterovirus (EV) species, are the causative agents of severe respiratory infections among children and are linked to childhood asthma exacerbations. The RV-C have been refractory to structure determination because they are difficult to propagate in vitro. Here, we report the cryo-EM atomic structures of the full virion and native empty particle (NEP) of RV-C15a. The virus has 60 {"}fingers{"} on the virus outer surface that probably function as dominant immunogens. Because the NEPs also display these fingers, they may have utility as vaccine candidates. A sequence-conserved surface depression adjacent to each finger forms a likely binding site for the sialic acid on its receptor. The RV-C, unlike other EVs, are resistant to capsid-binding antiviral compounds because the hydrophobic pocket in VP1 is filled with multiple bulky residues. These results define potential molecular determinants for designing antiviral therapeutics and vaccines.",

keywords = "Rhinovirus c|cryoelectron microscopy|atomic structure|asthma",

author = "Yue Liu and Hill, {Marchel G.} and Thomas Klose and Zhenguo Chen and Kelly Watters and Bochkov, {Yury A.} and Wen Jiang and Palmenberg, {Ann C.} and Rossmann, {Michael G.}",

note = "Funding Information: ACKNOWLEDGMENTS. We thank Roland Rueckert for critically reading the manuscript, Guimei Yu for helpful discussions, Valorie Bowman of the Purdue University Cryo-EM Facility and Ken Hibler of the FEI Company for technical assistance, and Sheryl Kelly for help preparing this manuscript. This work was supported by NIH Grants R37 AI011219 (to M.G.R.) and U19 AI104317 (to A.C.P.).",

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AU - Hill, Marchel G.

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AU - Watters, Kelly

AU - Bochkov, Yury A.

AU - Jiang, Wen

AU - Palmenberg, Ann C.

AU - Rossmann, Michael G.

N1 - Funding Information: ACKNOWLEDGMENTS. We thank Roland Rueckert for critically reading the manuscript, Guimei Yu for helpful discussions, Valorie Bowman of the Purdue University Cryo-EM Facility and Ken Hibler of the FEI Company for technical assistance, and Sheryl Kelly for help preparing this manuscript. This work was supported by NIH Grants R37 AI011219 (to M.G.R.) and U19 AI104317 (to A.C.P.).

PY - 2016/8/9

Y1 - 2016/8/9

N2 - Isolates of rhinovirus C (RV-C), a recently identified Enterovirus (EV) species, are the causative agents of severe respiratory infections among children and are linked to childhood asthma exacerbations. The RV-C have been refractory to structure determination because they are difficult to propagate in vitro. Here, we report the cryo-EM atomic structures of the full virion and native empty particle (NEP) of RV-C15a. The virus has 60 "fingers" on the virus outer surface that probably function as dominant immunogens. Because the NEPs also display these fingers, they may have utility as vaccine candidates. A sequence-conserved surface depression adjacent to each finger forms a likely binding site for the sialic acid on its receptor. The RV-C, unlike other EVs, are resistant to capsid-binding antiviral compounds because the hydrophobic pocket in VP1 is filled with multiple bulky residues. These results define potential molecular determinants for designing antiviral therapeutics and vaccines.

AB - Isolates of rhinovirus C (RV-C), a recently identified Enterovirus (EV) species, are the causative agents of severe respiratory infections among children and are linked to childhood asthma exacerbations. The RV-C have been refractory to structure determination because they are difficult to propagate in vitro. Here, we report the cryo-EM atomic structures of the full virion and native empty particle (NEP) of RV-C15a. The virus has 60 "fingers" on the virus outer surface that probably function as dominant immunogens. Because the NEPs also display these fingers, they may have utility as vaccine candidates. A sequence-conserved surface depression adjacent to each finger forms a likely binding site for the sialic acid on its receptor. The RV-C, unlike other EVs, are resistant to capsid-binding antiviral compounds because the hydrophobic pocket in VP1 is filled with multiple bulky residues. These results define potential molecular determinants for designing antiviral therapeutics and vaccines.

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Atomic structure of a rhinovirus C, a virus species linked to severe childhood asthma

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