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| Title | Molecular basis for the acid-initiated uncoating of human enterovirus D68. |
|---|---|
| Journal, issue, pages | Proc Natl Acad Sci U S A, Vol. 115, Issue 52, Page E12209-E12217, Year 2018 |
| Publish date | Dec 26, 2018 |
Authors | Yue Liu / Ju Sheng / Arno L W van Vliet / Geeta Buda / Frank J M van Kuppeveld / Michael G Rossmann / ![]() |
| PubMed Abstract | Enterovirus D68 (EV-D68) belongs to a group of enteroviruses that contain a single positive-sense RNA genome surrounded by an icosahedral capsid. Like common cold viruses, EV-D68 mainly causes ...Enterovirus D68 (EV-D68) belongs to a group of enteroviruses that contain a single positive-sense RNA genome surrounded by an icosahedral capsid. Like common cold viruses, EV-D68 mainly causes respiratory infections and is acid-labile. The molecular mechanism by which the acid-sensitive EV-D68 virions uncoat and deliver their genome into a host cell is unknown. Using cryoelectron microscopy (cryo-EM), we have determined the structures of the full native virion and an uncoating intermediate [the A (altered) particle] of EV-D68 at 2.2- and 2.7-Å resolution, respectively. These structures showed that acid treatment of EV-D68 leads to particle expansion, externalization of the viral protein VP1 N termini from the capsid interior, and formation of pores around the icosahedral twofold axes through which the viral RNA can exit. Moreover, because of the low stability of EV-D68, cryo-EM analyses of a mixed population of particles at neutral pH and following acid treatment demonstrated the involvement of multiple structural intermediates during virus uncoating. Among these, a previously undescribed state, the expanded 1 ("E1") particle, shows a majority of internal regions (e.g., the VP1 N termini) to be ordered as in the full native virion. Thus, the E1 particle acts as an intermediate in the transition from full native virions to A particles. Together, the present work delineates the pathway of EV-D68 uncoating and provides the molecular basis for the acid lability of EV-D68 and of the related common cold viruses. |
External links | Proc Natl Acad Sci U S A / PubMed:30530701 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 2.17 - 3.75 Å |
| Structure data | EMDB-7567, PDB-6crp: EMDB-7569, PDB-6crr: EMDB-7571, PDB-6crs: EMDB-7572, PDB-6cru: EMDB-7583, PDB-6cs3: EMDB-7589, PDB-6cs4: EMDB-7592, PDB-6cs5: EMDB-7593, PDB-6cs6: EMDB-7598, PDB-6csa: EMDB-7599, PDB-6csg: EMDB-7600, PDB-6csh: ![]() EMDB-9053: ![]() EMDB-9054: EMDB-9055, PDB-6mzi: ![]() EMDB-9056: ![]() EMDB-9057: ![]() EMDB-9058: ![]() EMDB-9059: ![]() EMDB-9060: |
| Chemicals | ![]() ChemComp-HOH: |
| Source |
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Keywords | VIRUS / genome release / acid |
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enterovirus d68
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