Download MendeleyMolecular basis for the acid-initiated uncoating of human enterovirus D68.
Liu, Y., Sheng, J., van Vliet, A.L.W., Buda, G., van Kuppeveld, F.J.M., Rossmann, M.G.(2018) Proc Natl Acad Sci U S A 115: E12209-E12217
- PubMed: 30530701
- DOI: https://doi.org/10.1073/pnas.1803347115
- Primary Citation of Related Structures:
6CRP, 6CRR, 6CRS, 6CRU, 6CS3, 6CS4, 6CS5, 6CS6, 6CSA, 6CSG, 6CSH, 6MZI - 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 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-? 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.
Organizational Affiliation:
Department of Biological Sciences, Purdue University, West Lafayette, IN 47907.
