First 3D movie of virus depicts key biological processes in replication

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Researchers from the University of Wisconsin-Milwaukee (UWM; WI, USA) have produced a 3-dimensional movie that displays a virus preparing to infect a healthy cell.

They captured millions of individual snapshots of a PR772 virus in unknown orientations and states by using the brightest and quickest imaging equipment available, known as x-ray free electron laser (XFEL). This method combines concepts from machine learning, differential geometry, graph theory and diffraction physics to create an algorithm that is capable of reconstructing sequential images.

Abbas Ourmazd (UWM), an author of the study published in Nature Methods, explained: “In the past, scientists have tried to infer what’s happening in a molecular-scale biological process by looking at a still photo at the start and a still photo at the end of a process. But you then don’t know what happens in between. With this method, we are in a position to watch biological machines perform their functions.”

Viral replication occurs when a virus invades a healthy cell – the virus then releases its DNA into the host cell and effectively hijacks the cell’s machinery in order to fabricate copies of itself. Viral progenies are then expelled to infect other cells.

Results from the study indicated that: “A single conformational coordinate controls reorganization of the genome, growth of a tubular structure from a portal vertex and release of the genome.” Thus, not only were researchers able to show how these events unfold, but also that reorganization of the virus’ genome and the formations of a tubular structure are not independent events; they are part of a concerted simultaneous process.

Brenda Hogue (Arizona State University, AZ, USA) described this finding as: “a new approach to understanding the changes that viruses undergo during infection.”

More than five years ago, Ahmad Hosseinizadeh (UWM), a senior researcher and first author of the study, began working on the algorithm needed to turn noisy XFEL snapshots into still 3D images. From there, progress was made through collaboration with scientists from different backgrounds.

Peter Schwander (UWM) explains: “We’ve been developing algorithms to reconstruct images in the correct order since 2009, so the UWM team was well-positioned to perform such an analysis. But it was difficult. We were able to make it work by watching how the experiments are done and adapting the data science to the data.”

As a result, this research has the potential to fundamentally advance our understanding of how biological processes inside the cell work – which could lead to better treatment for the horde of human diseases caused by viruses.

The authors concluded within the study that: “These results demonstrate that single-particle x-ray scattering has the potential to shed light on key biological processes.”

Sources: Hosseinizadeh A, Mashayekhi G, Copperman J et al. Conformational landscape of a virus by single-particle x-ray scattering. Nat. Methods doi:10.1038/nmeth.4395 (2017) (Epub ahead of print); www.eurekalert.org/pub_releases/2017-08/uow–nsr081117.php

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