Cell: Analyze the latest portrait of HIV virus to promote the development of AIDS vaccine

AIDS (AIDS) is a highly harmful infectious disease caused by human immunodeficiency virus (HIV) infection.

From this point of view, the AIDS epidemic situation in the world is not optimistic.

Recently, researchers from the University of Washington and the Scripps Institute published a research paper in the journal Cell entitled: Cryo-ETof Env on intact HIV virions reveals structural variation and positioning on the Gag lattice

The study uncovered new details about the human immunodeficiency virus (HIV) using powerful tools and techniques developed in the field of structural biology

The envelope glycoprotein (Env) on the surface of HIV-1 virus is an important viral entry protein machinery that mediates binding to host cell receptors and subsequent membrane fusion

More importantly, as the sole target of neutralizing antibodies, Env is also uniquely important to vaccine design efforts

To understand how Env is assembled on viral particles and how it differs structurally from soluble trimers, the research team studied immature and mature Gag-bearing HIV-1 virus-like particles (VLPs) on The envelope glycoproteins were subjected to cryo-electron tomography (cryo-ET), and subchromatographic averaging and structural mass spectrometry were performed

Structural analysis of the envelope protein (Env) of HIV virus-like particles (hVLPs)

These detailed findings include the location and 3D view of the structure of the viral envelope "spike" protein throughout the virus

"We're looking at the entire virus particle, and how the proteins on the surface are connected to the rest of the virus, and by looking at the intact virus structure, we can see this' How the different sides of the virus' face are displayed and how they are recognized or hidden by the immune system

Localization of hVLP-Env on the immature Gag lattice

This complete portrait of the HIV-1 virus structure also gave scientists new insights into the localization of the envelope spike protein on the virus's surface

Another previously unobserved finding is that the "stalk" that supports the envelope protein is flexible and can be tilted, presenting both an opportunity and a challenge for the immune system's neutralizing antibodies that protect cells from infection

Conformational changes in the central helical bundle (HR1-C) of hVLP-Env

In fact, targeting the HIV virus's envelope as a vaccine development target has been particularly difficult because the virus has few spike proteins and camouflages them with sugar molecules to evade the body's immune system

Extensive glycan shielding in hVLP-Env

Kelly Lee said: "This is a problem that HIV vaccine developers have been grappling with from the very beginning - the HIV virus mutates at a very rapid rate

In fact, just this February, a more deadly strain of HIV was discovered in the Netherlands (detail: A more severe, faster-spreading mutant strain of HIV has emerged) Fortunately, even though the strain is a "highly" deadly new variant", but it still responds to existing HIV treatment regimens

Original source:

Vidya Mangala Prasad, et al.