The emergence in 2003 of a new coronavirus (CoV) responsible for the atypical pneumonia termed severe acute respiratory syndrome (SARS) was a stark reminder that hitherto unknown viruses have the potential to cross species barriers to become new human pathogens. Here we describe the SARS-CoV 'spike' structure determined by single-particle cryo-EM, along with the docked atomic structures of the receptor-binding domain and prefusion core.
Genome sequences of chicken (low pathogenic avian influenza [LPAI] and highly pathogenic avian influenza [HPAI]) and human isolates from a 2004 outbreak of H7N3 avian influenza in Canada showed a novel insertion in the HA0 cleavage site of the human and HPAI isolate. This insertion likely occurred by recombination between the hemagglutination and matrix genes in the LPAI virus.
Presentation in pediatric patients with allergic fungal sinusitis is different from that in adults, with children having obvious abnormalities of their facial skeleton, unilateral sinus disease, and asymmetrical disease more often. Findings on computed tomography scan show an equal amount of bony erosion with extension of disease. The types of fungus cultured in the sinus cavities are similar in both groups.
The SARS coronavirus (SARS-CoV) spike is the largest known viral spike molecule, and shares a similar function with all class 1 viral fusion proteins. Previous structural studies of membrane fusion proteins have largely used crystallography of static molecular fragments, in isolation of their transmembrane domains. In this study we have produced purified, irradiated SARS-CoV virions that retain their morphology, and are fusogenic in cell culture. We used cryo-electron microscopy and image processing to investigate conformational changes that occur in the entire spike of intact virions when they bind to the viral receptor, angiotensin-converting enzyme 2 (ACE2). We have shown that ACE2 binding results in structural changes that appear to be the initial step in viral membrane fusion, and precisely localized the receptor-binding and fusion core domains within the entire spike. Furthermore, our results show that receptor binding and subsequent membrane fusion are distinct steps, and that each spike can bind up to three ACE2 molecules. The SARS-CoV spike provides an ideal model system to study receptor binding and membrane fusion in the native state, employing cryo-electron microscopy and single-particle image analysis.
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