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Scientists in the Netherlands reveal 3-D structure of coronavirus

A study by EU-funded researchers in the Netherlands has uncovered the three-dimensional structure of the coronavirus, a pathogen implicated in severe acute respiratory syndrome (SARS) and the common cold. Their findings, which were made possible by an imaging technique called ...

A study by EU-funded researchers in the Netherlands has uncovered the three-dimensional structure of the coronavirus, a pathogen implicated in severe acute respiratory syndrome (SARS) and the common cold. Their findings, which were made possible by an imaging technique called cryo-electron tomography, provide valuable new insights into the nature of the virus previously unattainable using conventional, two-dimensional imaging methods. The research, published in the Proceedings of the National Academy of Sciences (PNAS), was funded in part by a Marie Curie Intra-European Fellowship from the EU. Coronaviruses (CoV) are involved in inflammation of both the upper respiratory and gastrointestinal tracts of animals and birds. They are believed to cause many types of colds in humans, have been widely publicised as a factor in SARS and are also behind a number of diseases in farm animals. Understanding the structure of the virus is essential to uncovering ways to treat these types of infection. Scientists in the current study examined the mouse hepatitis virus (MHV), a well-studied virus which is considered to be a 'prototypic' CoV. The decision to study MHV was important because the shape and size of many CoVs change at different stages of the cell's lifecycle; the size and shape of MHV cells, in contrast, are more consistent. The scientists used cryo-electron tomography, fixing the particles by 'plunge-freezing' them. This allowed them to examine several slices of each virus (144 samples in total) in situ, and to reconstruct three-dimensional images of the virions that were not damaged by radiation or the effects of staining. One of the main findings of the study was that the envelopes surrounding the MHV particles were extraordinarily thick, around twice the size of a typical biological membrane. Also, the contents of MHV particles are extremely compacted. These and other factors have made examination of CoV's interior very difficult in the past; previous studies looked at contents that had been released from the interior, which could have been rearranged in the process. The scientists determined that the shape of MHV is distinctly spherical, with a limited number of 'spikes' (which make infection possible). It is covered in striations that they attribute to the actions of the M protein, which plays a role in establishing a virus's shape. Interestingly, they found that MHV's thick envelope has an extra layer next to the usual lipid bi-layer, made up of an extensively folded protein core rather than the expected 'shelled' core. They also observed several 'interaction sites' that are important to MHV's structure. 'Actually, the interior of MHV as revealed in this study shows remarkable analogy with that of influenza A virions,' the study reads. 'Yet, these viruses are different in many respects.' MHV's interior has a flexible structure that extensively twists and folds in upon itself, they conclude, which would make it impossible to recognise using two-dimensional imaging. Deciphering the structure of MHV will, the authors hope, enable better modelling of the viral genome, leading to a more complete understanding of all coronaviruses.

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