Human Gut Virus Mapped for First Time by Researchers

Researchers at APC Microbiome Ireland (APC) have collaborated with scientists at the University of York to complete the first-ever structural atlas of crassvirales (also referred to as crassvirales, phage, phage-like) – the most abundant group of viruses in the world. human gut, which can play an important role in shaping the gut microbiome, and influencing health and disease.

For the first time, scientists have grown cruciferous virus in the lab and developed a detailed, atomic-level structure of a gut virus. These gut viruses are thought to play a role in shaping the composition and function of the human microbiome. The ability to grow them in the laboratory, together with this newly generated structural atlas, will facilitate the research needed to investigate their roles in microbiome functions and human health. The study has been published in the journal nature.

Key achievements include identifying the presence of several cargo proteins carried by the virus, including finding a protein that occupies both the head and tail of the virus. This discovery allows the team to predict a mechanism for how the virus will inject its DNA into its bacterial target.

A new protein fold has also been identified that acts as a ‘gatekeeper’ – controlling what gets transported in and out of viral particles. In addition, the team is now able to assign functions to viral genes that have so far been classified as hypothetical.

Professor Colin Hill, co-lead author of the study and founding principal investigator at APC, said, “These viruses are probably the most abundant biological entities associated with humans, yet we only found out about them less than a decade ago, so this is all a very beautiful and exciting novel.” .

“Growing the virus is a major research milestone and breakthrough. Essentially, you have to be able to grow it to identify it, and once we developed the ability to grow the virus here at APC, we were able to reach out to colleagues in York to help study it in all its fascinating detail. The final structure is beautiful. Truly and a fitting reward for years of meticulous work at both APC and York”, stated Professor Colin Hill.

“This study underscores why it is still important to make the necessary effort to study viruses in the lab. We can learn a lot from DNA sequencing and computational biology, but you really need to grow a virus in the lab to fully understand it and to inform future experiments,” added Andre N. Shkoborov, study co-principal investigator at APC.

Researchers at APC have been studying gut viromes for more than a decade and have contributed greatly to the knowledge of so many viruses. The alimentary canal found in the digestive system varies across human cultures, lifestyles, and locations. Professor Shkoborov plans to continue studying enteroviruses, including the possible role of bacterial viruses in the spread of antibiotic resistance.

Initially, researchers only knew of the existence of the crassvirus by analyzing DNA sequences taken from gut samples, but a major breakthrough was made in 2018 when a team of scientists including Andrey Shkoporov, Professor Colin Hill, Ekaterina Khokhlova and others at APC Microbiome Ireland grew And the School of Microbiology at UCC is a member of the crass virus for the first time. This enabled the research team to collaborate with Professor Fred Antson and Dr Oliver Bayfield at the University of York to further investigate the virus using cryo-EM (cryo-electron microscopy) to comprehensively map the 1,440 proteins that make up the viral particle.

Professor John F Cryan, UCC Vice President for Research and Innovation and Principal Investigator at APC Microbiome Ireland, said, “Congratulations to Professor Colin Hill and Professor Andrey Shkoborov on this recent and important APC paper which provides detailed structure and function mapping of crassviruses, together with comparative sequence analysis. , allows us to assign functions to the majority of previously uncharacterized proteins involved in virus assembly and infection.”