In a groundbreaking collaboration, researchers at APC Microbiome Ireland (APC) and the University of York have completed the first-ever structural atlas of a crassvirus, a type of virus abundant in the human gut that can impact health and disease by shaping the gut microbiome.
For the first time, scientists have successfully grown a crassvirus in a lab and created a detailed atomic-level structure of this gut virus. This achievement is expected to facilitate research aimed at understanding the role of these gut viruses in shaping the composition and functionality of the human microbiome and their impact on human health. The study has been published in the prestigious journal Nature.
The study's key breakthroughs include identifying the presence of multiple cargo proteins carried by the virus, including a protein that occupies both the head and tail of the virus, enabling the team to predict how the virus injects its DNA into its bacterial target.
Furthermore, the researchers discovered a new protein fold that acts as a gatekeeper, regulating what enters and exits the viral particle. Additionally, they have assigned functions to viral genes that were previously designated as hypothetical.
Professor Colin Hill, co-lead study researcher and founding Principal Investigator in APC, said that these viruses are likely the most abundant biological entities associated with humans, and the team's findings are highly exciting given how little was known about them until recently.
Professor Colin Hill of APC Microbiome Ireland has hailed the ability to grow crassviruses in a lab as a significant breakthrough in research. According to Hill, the ability to cultivate the virus has enabled his team and colleagues at the University of York to study it in unprecedented detail, culminating in the creation of a “truly beautiful” atomic-level structure. Hill also noted that lab-grown viruses are essential to fully understand their nature, despite the insights offered by DNA sequencing and computational biology.
Co-lead researcher Andrey N. Shkoporov echoed Hill's sentiment, stressing the importance of in-lab virus growth to inform future experiments. APC has been investigating the gut virome for more than a decade, contributing extensively to knowledge of these highly diverse viruses in the gastrointestinal tract. Shkoporov intends to keep studying the gut virome, focusing on the potential role of bacterial viruses in the spread of antibiotic resistance.
A research team at APC Microbiome Ireland and the School of Microbiology at UCC achieved a major breakthrough in 2018 when they successfully grew a member of the crassvirus for the first time. The team, which included Andrey Shkoporov, Professor Colin Hill, and Ekaterina Khokhlova, then collaborated with Professor Fred Antson and Dr. Oliver Bayfield at the University of York to investigate the virus in greater detail. Using cryo-electron microscopy technology, they mapped out the 1,440 proteins that make up the viral particle.
UCC Vice President for Research and Innovation and APC Microbiome Ireland Principal Investigator, Professor John F. Cryan, congratulated Professors Hill and Shkoporov on the significant achievement, which involved a detailed structure-function mapping of crassviruses. The study also allowed the team to assign functions to previously uncharacterized proteins involved in virion assembly and infection, thanks to comparative sequential analysis.