Enterovirus 71 (EV71), a major agent of hand-foot-and-mouth disease in children, can cause severe central nervous system disease and mortality. At present no vaccine or antiviral therapy is available. We have determined high-resolution structures for the mature virus and natural empty particles. The structure of the mature virus is similar to that of other enteroviruses, whilst the empty particles are dramatically expanded, with notable fissures, resembling elusive enterovirus uncoating intermediates not previously characterized in atomic detail. Hydrophobic capsid pockets within the EV71 capsid are collapsed in this expanded particle, providing a detailed explanation of the mechanism for receptor-binding triggered virus uncoating. The results provide a paradigm for enterovirus uncoating, in which the VP1 GH loop acts as an adaptor-sensor for the attachment of cellular receptors, converting heterologous inputs to a generic uncoating mechanism, spotlighting novel points for therapeutic intervention.

We present a study of molecular outflows toward a sample of 69 luminous IRAS point sources. The sample is associated with dense molecular gas and has far-infrared luminosities ranging from 10 2 to 10 5 L , indicating these objects as regions likely forming high-mass stars. Mapping in the CO J ¼ 2 1 line shows that molecular outflows are ubiquitous in these regions. Most of the outflows have masses of tens of M . The typical dynamical timescale of the flow, without correcting for inclination of the flow axis, is a few times 10 4 yr. The typical energy in the outflows is 10 46 ergs, comparable to the turbulent energy in the core. Nearly half of the outflows show spatially resolved bipolar lobes. This indicates that low-mass young stars that coexist in the region are not responsible for the bipolar outflows observed. It is the more massive stars that drive the outflow. The large detection rate of outflows in the region favors an accretion process in the formation of massive stars. The maximum mass-loss rate in the wind is about 10 À4 M yr À1 . If these outflows are driven via accretion, the accretion rate should be as high as a few times 10 À4 M yr À1

The EV71 vaccine provided protection against EV71-associated hand, foot, and mouth disease or herpangina in infants and young children. (Funded by Sinovac Biotech; ClinicalTrials.gov number, NCT01507857.).

It remains largely mysterious how the genomes of non-enveloped eukaryotic viruses are transferred across a membrane into the host cell. Picornaviruses are simple models for such viruses, and initiate this uncoating process through particle expansion, which reveals channels through which internal capsid proteins and the viral genome presumably exit the particle, although this has not been clearly seen until now. Here we present the atomic structure of an uncoating intermediate for the major human picornavirus pathogen CAV16, which reveals VP1 partly extruded from the capsid, poised to embed in the host membrane. Together with previous low-resolution results, we are able to propose a detailed hypothesis for the ordered egress of the internal proteins, using two distinct sets of channels through the capsid, and suggest a structural link to the condensed RNA within the particle, which may be involved in triggering RNA release.