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A detailed image at near-atomic levels of the BK polyomavirus (BKV), which affects kidney and bone marrow transplant patients, is now available for the first time.
This molecular-level structural visualization could allow scientists to study potential targets for antiviral therapies or drugs.
Approximately 80% to 90% of the general population are seropositive for the most prevalent BKV genotypes. Yet the virus rarely causes illness in people with healthy immune systems.
But the BKV causes nephropathy and hemorrhagic cystitis in immunosuppressed patients. Currently, no effective antiviral agents are available specifically targeting BKV.
Using high-resolution cryoelectron microscopy (cryo-EM), the research team at the University of Leeds Astbury Centre for Structural Molecular Biology determined the structure of BKV at 3.8 Å resolution.
At this resolution, they could highlight differences between human BKV and BKV pathogens that infect simian and murine hosts.
The investigators created the structures by freezing infectious BKV particles and taking thousands of images using the microscopes. The two-dimensional images were then combined computationally to produce a high-resolution, three-dimensional view of the virus.
They reported their findings in the journal Structure.
Senior investigator Neil A. Ranson, PhD, of the University of Leeds , noted that cryo-EM has been around for 30 years.
Although it’s been useful, the technology lacked the ability to routinely look at molecules at the level of detail needed, he said.
"However, the Titan Krios microscopes we have installed in Leeds are absolutely state-of-the-art and mean that these limitations have been shattered. Researchers and industry users who work with us can now image biological molecules with an incredible resolution. “
The investigators believe the quality and completeness of the cryo-EM structures they captured allows researchers to describe the various conformations of the C termini of the major capsid protein VP1, which play a fundamental role in the assembly and stability of a polyomavirus capsid.
The investigators say the images also present a more complete picture of disulfide bonding in the capsid.
Thus, the images provide insights into the structure of the human pathogen at near native conditions and give scientists a better-quality research tool to use.
“Crucially, we'll also be able to see how these molecules interact with each other," Dr Ransom said.
The BK Polyomavirus structure research was funded by Wellcome, Kidney Research UK, and Kidney Research Yorkshire.
A detailed image at near-atomic levels of the BK polyomavirus (BKV), which affects kidney and bone marrow transplant patients, is now available for the first time.
This molecular-level structural visualization could allow scientists to study potential targets for antiviral therapies or drugs.
Approximately 80% to 90% of the general population are seropositive for the most prevalent BKV genotypes. Yet the virus rarely causes illness in people with healthy immune systems.
But the BKV causes nephropathy and hemorrhagic cystitis in immunosuppressed patients. Currently, no effective antiviral agents are available specifically targeting BKV.
Using high-resolution cryoelectron microscopy (cryo-EM), the research team at the University of Leeds Astbury Centre for Structural Molecular Biology determined the structure of BKV at 3.8 Å resolution.
At this resolution, they could highlight differences between human BKV and BKV pathogens that infect simian and murine hosts.
The investigators created the structures by freezing infectious BKV particles and taking thousands of images using the microscopes. The two-dimensional images were then combined computationally to produce a high-resolution, three-dimensional view of the virus.
They reported their findings in the journal Structure.
Senior investigator Neil A. Ranson, PhD, of the University of Leeds , noted that cryo-EM has been around for 30 years.
Although it’s been useful, the technology lacked the ability to routinely look at molecules at the level of detail needed, he said.
"However, the Titan Krios microscopes we have installed in Leeds are absolutely state-of-the-art and mean that these limitations have been shattered. Researchers and industry users who work with us can now image biological molecules with an incredible resolution. “
The investigators believe the quality and completeness of the cryo-EM structures they captured allows researchers to describe the various conformations of the C termini of the major capsid protein VP1, which play a fundamental role in the assembly and stability of a polyomavirus capsid.
The investigators say the images also present a more complete picture of disulfide bonding in the capsid.
Thus, the images provide insights into the structure of the human pathogen at near native conditions and give scientists a better-quality research tool to use.
“Crucially, we'll also be able to see how these molecules interact with each other," Dr Ransom said.
The BK Polyomavirus structure research was funded by Wellcome, Kidney Research UK, and Kidney Research Yorkshire.
A detailed image at near-atomic levels of the BK polyomavirus (BKV), which affects kidney and bone marrow transplant patients, is now available for the first time.
This molecular-level structural visualization could allow scientists to study potential targets for antiviral therapies or drugs.
Approximately 80% to 90% of the general population are seropositive for the most prevalent BKV genotypes. Yet the virus rarely causes illness in people with healthy immune systems.
But the BKV causes nephropathy and hemorrhagic cystitis in immunosuppressed patients. Currently, no effective antiviral agents are available specifically targeting BKV.
Using high-resolution cryoelectron microscopy (cryo-EM), the research team at the University of Leeds Astbury Centre for Structural Molecular Biology determined the structure of BKV at 3.8 Å resolution.
At this resolution, they could highlight differences between human BKV and BKV pathogens that infect simian and murine hosts.
The investigators created the structures by freezing infectious BKV particles and taking thousands of images using the microscopes. The two-dimensional images were then combined computationally to produce a high-resolution, three-dimensional view of the virus.
They reported their findings in the journal Structure.
Senior investigator Neil A. Ranson, PhD, of the University of Leeds , noted that cryo-EM has been around for 30 years.
Although it’s been useful, the technology lacked the ability to routinely look at molecules at the level of detail needed, he said.
"However, the Titan Krios microscopes we have installed in Leeds are absolutely state-of-the-art and mean that these limitations have been shattered. Researchers and industry users who work with us can now image biological molecules with an incredible resolution. “
The investigators believe the quality and completeness of the cryo-EM structures they captured allows researchers to describe the various conformations of the C termini of the major capsid protein VP1, which play a fundamental role in the assembly and stability of a polyomavirus capsid.
The investigators say the images also present a more complete picture of disulfide bonding in the capsid.
Thus, the images provide insights into the structure of the human pathogen at near native conditions and give scientists a better-quality research tool to use.
“Crucially, we'll also be able to see how these molecules interact with each other," Dr Ransom said.
The BK Polyomavirus structure research was funded by Wellcome, Kidney Research UK, and Kidney Research Yorkshire.