Unexpected findings detailed in a new portrait of HIV revealing the structure of the virus

A cryogenic electron microscope was used to collect 3D images of almost complete HIV virus particles. These studies provided a detailed portrait of the Env glycoprotein (blue), the antigenic face that HIV presents to the immune system, revealing new aspects of how it is present on the surface of the virus. .. Credits: Kelly Lee / Lee Lab, University of Washington

Researchers at the University of Washington and the Scripps Institute have discovered new details about the human immunodeficiency virus HIV, using powerful tools and techniques developed in the field of structural biology. The findings focus on the basic architecture just above and below the surface of the virus and may help in the design and development of vaccines that can protect against AIDS.

These detailed findings include the viral envelope “peplomer” protein (Env). protein, Used when the virus binds to cells) in the context of a complete virus. Researchers typically view protein particles isolated from the virus, or expressed as engineered or purified proteins.In another important development, scientists shed new light on Glycan shield— A protein sugar that can hide it from the body’s immune system.

“We are investigating how this protein on the surface of the entire virus particle is associated with the rest of the virus,” said Kelly Lee, an associate professor of medicinal chemistry at UW Pharmacy. I am. “And if you look at the intact viral structure, you can see how the various aspects of this” viral face “are displayed, recognized by, or hidden from the immune system. “

This intact view of the virus also allowed scientists to gain new insights into the positioning of the envelope. Spike protein On the surface associated with internal protein structures called the Gag lattice.

“This finding overturns previous models of how parts of the virus are assembled and helps us focus our attention on where the docking interactions of these two proteins are likely to be. “I will.” Lee said. “This interaction needs to be resolved in more detail, but at least the current work will give us the correct architectural model of the virus assembly.”

It was this particular finding that led to the title of the paper — “Env’s Cryo-ET on an intact HIV billion reveals structural changes and position on the gag grid” — published in the journal on February 4th. it was done cell.. Another discovery previously unobserved by scientists is that the “stems” that support enveloped proteins can be flexible and tilted, giving opportunities and challenges to neutralizing antibodies in the immune system that protect cells from infection. Is to bring both.

Unexpected findings detailed in a new portrait of HIV

The figure shows how the two key parts of the virus, the Env surface protein and the internal Gag assembly, are organized together within the newly assembled immature virus particles. This interaction is essential for the formation of new HIV virus particles, and further understanding of it may indicate ways to block the interaction and inhibit viral production. Credits: Kelly Lee / Lee Lab, University of Washington

“Structural biology has driven the design of HIV vaccines, so a better understanding of what we are aiming for could drive innovation and improve vaccines,” said Associate of Immunology. Professor and co-author Michael Zwick said. Microbiology at Scripps Research Institute.

The HIV envelope presents a particularly difficult target for vaccine development, as the virus shows few spikes and camouflages them with sugar molecules to evade the immune system.

“All these functions increase the dynamic variability that HIV peplomers present to the immune system,” said Lee, who directs the UW Lab to investigate the structure and dynamics of the virus. “This is something that people developing HIV vaccines have been working on from the beginning. virus Astronomically and rapidly change and change itself. Each time an individual is infected, there are literally thousands of different variants within that individual, and the entire population grows even more. ”

In fact, in February, an even more deadly HIV strain was found to be endemic in the Netherlands. Fortunately, this strain is a “very toxic mutant”, but it still responds to treatment.

“This is a reminder that these viruses are constantly changing, so scientists need to keep studying them,” Zwick said.

The co-author is Vidya Mangala Prasad, a former acting instructor at the UW Pharmacy currently at the Institute of Science of India. Daniel Lehman, Department of Immunology and Microbiology, Scripps Research Institute. Department of Medicinal Chemistry of Klaus Lovendahl, Jacob Croft, Edgar Hodge, UW School of Pharmacy. Mark Benheim was involved in the project as a graduate student at the University of Washington.

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For more information:
Vidya Mangala Prasad et al, Cryo-ET of Env on intact HIV virions reveals structural changes and positions on the Gag lattice. cell (2022). DOI: 10.1016 / j.cell.2022.01.013

Journal information:

Quote: Unexpected discoveries detailed in the new portrait of HIV revealing the virus architecture (February 16, 2022) https: // -Obtained from virus.html on February 16, 2022

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Unexpected findings detailed in a new portrait of HIV revealing the structure of the virus

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