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Unexpected findings are described in detail in a new portrait of HIV, which reveals the architecture of the virus

Cryoelectron microscopy was used to collect three-dimensional images of almost complete HIV particles. Studies provide a detailed portrait of the antigenic person, the glycoprotein Env (blue), which HIV represents to the immune system, and have revealed new aspects of how it exists on the surface of the virus. Credit: Kelly Lee / Lee Laboratory at the University of Washington

Using powerful tools and techniques developed in structural biology, researchers from the University of Washington and the Scripps Research Institute have discovered new details about the human immunodeficiency virus, HIV. The findings are of interest to the basic architecture of the virus above and below its surface and may help in the design and development of a vaccine that can protect against AIDS.


These detailed findings include three-dimensional views of the structure and position of the proteins of the envelope of the virus “thorn” (Env protein, used when the virus binds to cells) in the context of a complete virus. Typically, researchers consider protein particles separated from the virus or expressed as engineered or purified proteins. In another key development, scientists shed new light on glycan shields-sugar in proteins that can hide it from the body’s immune system.

“We look at the virus particle as a whole and how this protein on the surface compares to the rest of the virus,” said lead author Kelly Lee, an associate professor of medical chemistry at UW School of Pharmacy. “And looking at the intact structure of the virus, we can see how different facets of this ‘virus face’ are reflected and how they will be recognized or hidden from the immune system.”

This pristine species of virus has also allowed scientists to gain a new understanding of the location of the shell protein thorns on the surface relative to an internal protein structure called the Gag lattice.

“This discovery overturns previous models of collecting parts of viruses and helps focus our focus on where these two proteins may interact,” Lee said. “This interaction needs to be addressed in more detail, but at least the current work gives us the right architectural model to build the virus.”

It is this conclusion that led to the title of the article – “Cryo-ET Env on intact HIV virions shows structural variations and location on the Gag lattice” – published February 4 in the journal Cell. Another finding that has not been observed before, the researchers noted, is that the “stem” that supports the protein shell is flexible and can be tilted, creating both opportunities and challenges for neutralizing immune system antibodies that protect cells from infection.

Unexpected findings are described in detail in the new HIV portrait

The figure illustrates how the two key parts of the virus, the Env surface protein and the internal Gag assembly, are organized relative to each other in newly collected immature virus particles. This interaction is crucial for the formation of new HIV particles, and a more detailed understanding of this may indicate ways to block the interaction and inhibit virus production. Credit: Kelly Lee / Lee Laboratory at the University of Washington

“Structural biology has stimulated the development of HIV vaccines, because we get a better and better idea of ​​what we are focusing on, what inspires innovation and can improve vaccines,” said Michael Zwick, associate professor of immunology. and Microbiology at the Scripps Research Institute.

Nail added that the HIV shell is a particularly difficult target for vaccine development because the virus detects so few thorns and masks them with sugar molecules to escape our immune system.

“All of these features increase the dynamic variability that the HIV protein represents to the immune system,” said Lee, who also runs the UW lab, which studies the structure and dynamics of the virus. “It’s something that people who are developing HIV vaccines have struggled with since the beginning virus mutates and changes astronomically and rapidly. Every time it infects an individual, you get literally thousands of different options in that individual, and if you look at the population, it multiplies even more. ”

In fact, it was discovered in February that an even more deadly strain of HIV was circulating in the Netherlands. Fortunately, although the strain is a “highly virulent option,” it is still treatable.

“It’s just another reminder that these viruses are always changing, so we need scientists to continue studying them,” Zwick said.

Co-authors are Vidya Mangala Prasad, a former acting instructor at the UW School of Pharmacy, now at the Indian Institute of Science; Daniel Lyman, Department of Immunology and Microbiology, Scripps Research Institute; Klaus Lawndal, Jacob Croft and Edgar Hodge, Department of Medical Chemistry, UW School of Pharmacy; and Mark Benheim, who worked on the project as a UW graduate student.


The Omicron variant is more transmissible, but the vaccines are still effective


Additional information:
Vidya Mangala Prasad et al, Cryo-ET of Env on intact HIV virions shows structural variations and location on the Gag lattice, Cell (2022). DOI: 10.1016 / j.cell.2022.01.013

Information about the magazine:
Cell

Citation: Unexpected findings are described in detail in the new HIV portrait showing the architecture of the virus (2022, February 16), obtained on February 16, 2022 from https://phys.org/news/2022-02-unexpected-portrait-hiv- revealing-virus.html

This document is subject to copyright. Except for any honest transaction for the purpose of private study or research, no part may be reproduced without written permission. The content is provided for informational purposes only.



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Unexpected findings are described in detail in a new portrait of HIV, which reveals the architecture of the virus

Cryoelectron microscopy was used to collect three-dimensional images of almost complete HIV particles. Studies provide a detailed portrait of the antigenic person, the glycoprotein Env (blue), which HIV represents to the immune system, and have revealed new aspects of how it exists on the surface of the virus. Credit: Kelly Lee / Lee Laboratory at the University of Washington

Using powerful tools and techniques developed in structural biology, researchers from the University of Washington and the Scripps Research Institute have discovered new details about the human immunodeficiency virus, HIV. The findings are of interest to the basic architecture of the virus above and below its surface and may help in the design and development of a vaccine that can protect against AIDS.


These detailed findings include three-dimensional views of the structure and position of the proteins of the envelope of the virus “thorn” (Env protein, used when the virus binds to cells) in the context of a complete virus. Typically, researchers consider protein particles separated from the virus or expressed as engineered or purified proteins. In another key development, scientists shed new light on glycan shields-sugar in proteins that can hide it from the body’s immune system.

“We look at the virus particle as a whole and how this protein on the surface compares to the rest of the virus,” said lead author Kelly Lee, an associate professor of medical chemistry at UW School of Pharmacy. “And looking at the intact structure of the virus, we can see how different facets of this ‘virus face’ are reflected and how they will be recognized or hidden from the immune system.”

This pristine species of virus has also allowed scientists to gain a new understanding of the location of the shell protein thorns on the surface relative to an internal protein structure called the Gag lattice.

“This discovery overturns previous models of collecting parts of viruses and helps focus our focus on where these two proteins may interact,” Lee said. “This interaction needs to be addressed in more detail, but at least the current work gives us the right architectural model to build the virus.”

It is this conclusion that led to the title of the article – “Cryo-ET Env on intact HIV virions shows structural variations and location on the Gag lattice” – published February 4 in the journal Cell. Another finding that has not been observed before, the researchers noted, is that the “stem” that supports the protein shell is flexible and can be tilted, creating both opportunities and challenges for neutralizing immune system antibodies that protect cells from infection.

Unexpected findings are described in detail in the new HIV portrait

The figure illustrates how the two key parts of the virus, the Env surface protein and the internal Gag assembly, are organized relative to each other in newly collected immature virus particles. This interaction is crucial for the formation of new HIV particles, and a more detailed understanding of this may indicate ways to block the interaction and inhibit virus production. Credit: Kelly Lee / Lee Laboratory at the University of Washington

“Structural biology has stimulated the development of HIV vaccines, because we get a better and better idea of ​​what we are focusing on, what inspires innovation and can improve vaccines,” said Michael Zwick, associate professor of immunology. and Microbiology at the Scripps Research Institute.

Nail added that the HIV shell is a particularly difficult target for vaccine development because the virus detects so few thorns and masks them with sugar molecules to escape our immune system.

“All of these features increase the dynamic variability that the HIV protein represents to the immune system,” said Lee, who also runs the UW lab, which studies the structure and dynamics of the virus. “It’s something that people who are developing HIV vaccines have struggled with since the beginning virus mutates and changes astronomically and rapidly. Every time it infects an individual, you get literally thousands of different options in that individual, and if you look at the population, it multiplies even more. ”

In fact, it was discovered in February that an even more deadly strain of HIV was circulating in the Netherlands. Fortunately, although the strain is a “highly virulent option,” it is still treatable.

“It’s just another reminder that these viruses are always changing, so we need scientists to continue studying them,” Zwick said.

Co-authors are Vidya Mangala Prasad, a former acting instructor at the UW School of Pharmacy, now at the Indian Institute of Science; Daniel Lyman, Department of Immunology and Microbiology, Scripps Research Institute; Klaus Lawndal, Jacob Croft and Edgar Hodge, Department of Medical Chemistry, UW School of Pharmacy; and Mark Benheim, who worked on the project as a UW graduate student.


The Omicron variant is more transmissible, but the vaccines are still effective


Additional information:
Vidya Mangala Prasad et al, Cryo-ET of Env on intact HIV virions shows structural variations and location on the Gag lattice, Cell (2022). DOI: 10.1016 / j.cell.2022.01.013

Information about the magazine:
Cell

Citation: Unexpected findings are described in detail in the new HIV portrait showing the architecture of the virus (2022, February 16), obtained on February 16, 2022 from https://phys.org/news/2022-02-unexpected-portrait-hiv- revealing-virus.html

This document is subject to copyright. Except for any honest transaction for the purpose of private study or research, no part may be reproduced without written permission. The content is provided for informational purposes only.



Reported by Source link

RELATED ARTICLES
- Advertisment -

Most Popular