In the game of evolution, viruses are among the most adaptable players, constantly changing in response to their environments. Researchers in immunology and structural biology regularly monitor these changes, especially those that could pose a threat to public health. Scientists use X-ray facilities like the Stanford Synchrotron Radiation Lightsource (SSRL) at the Department of Energy’s SLAC National Accelerator Laboratory to examine the underlying structures of individual proteins, which influence a virus’ behavior and ability to spread between species.
Since the first recorded case of highly pathogenic avian influenza H5N1 – commonly known as avian flu or bird flu – in 1996, Ian Wilson, professor of structural biology at Scripps Research, and his colleagues have been closely tracking the evolution of several key proteins using SSRL.
Recently, Wilson’s team investigated the evolution of a protein that plays a crucial role in H5N1’s ability to transmit between species. Their analysis found that the protein is susceptible to a mutation that could help the virus attach to human cells, potentially increasing the risk of human transmission. The findings – published in Proceedings of the National Academy of Sciences – underscore the need for ongoing monitoring of H5N1’s evolution.
“Facilities like SSRL enable research on infectious diseases and pandemic threats, accelerating our ability to respond to global health emergencies,” said Aina Cohen, division director of Structural Molecular Biology at SSRL. “Discoveries made in areas like drug development, vaccine design and diagnostics can lead to more effective treatments, earlier disease detection and stronger preventive measures.”
Studying proteins with SSRL
Though H5N1 viruses are prevalent in birds and some mammals around the world, transmission to and between humans is rare. However, this could change as the virus continues to mutate. Wilson’s team focuses on H5N1’s hemagglutinin (HA) protein, which enables the virus to attach to receptors on the surfaces of host cells. If this protein mutates from its current receptor specificity – which favors avian-type receptors – to one that effectively binds to human-type receptors, the potential for transmission to humans could rise significantly.
“Monitoring changes in receptor specificity – the way a virus recognizes host cells – is crucial because receptor binding is a key step toward transmissibility,” Wilson said. “That being said, receptor mutations alone don’t guarantee that the virus will transmit between humans.”
To build a timeline of the HA protein’s evolution, Wilson’s team analyzes proteins from samples collected in various years. These studies do not use live virus samples; instead, the research team generates proteins using data from the Global Initiative on Sharing All Influenza Data. The team then crystallizes these proteins and sends the crystallized samples to SSRL.
At SSRL’s Beam Line 12-1, the Scripps team collects data remotely with assistance from on-site scientists at SLAC. By analyzing how X-rays diffract when passing through the protein crystals, researchers can reconstruct the protein’s 3D structure, gaining insights into the behavior of various HA proteins.
“The bright X-ray microbeams produced by SSRL, combined with a high level of experimental automation and user-friendly experimental control interface, make Beam Line 12-1 a premiere resource for these types of experiments,” Cohen said. “With decades of experience, SSRL staff support our users, helping them achieve the highest quality data.”
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