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Author Topic: Mechanism by which protein on the surface of HIV evades attack from antibodies.  (Read 523 times)

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Offline Jim Allen

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Researchers have discovered the mechanism by which a vital three-part protein on the surface of HIV remains folded shut such that it can evade an attack from antibodies.

Considerable research has investigated the so-called Env protein on HIVís surface. Env is vital to HIVís lifecycle, as it attaches to receptors on immune cells so the virus can inject its genetic material and infect the cells. Env evades antibodies because of particulars of its three-part shape, known as a trimer.

The trimer can be open like a flower in bloom or closed like a flower still budding. When in the closed position, Env shelters the proteins, known as epitopes, that the immune system recognizes. Instead, the exterior of the trimer is sugar coated; the immune system does not recognize sugar as well as epitopes.

In a 2014 study, a team of scientists at the National Institute of Allergy and Infectious Diseases found that two amino acids (the building blocks of proteins) called tyrosines were instrumental in preventing Env from opening.

Publishing their findings in the journal Mbio, the scientists sought a more detailed understanding of the two key tyrosines in a new study. They genetically modified various HIV strains to express different amino acids, called alanine and phenylalanine, in place of the pair of tyorsines. The Envs on the surface of these mutant viruses did indeed remain open.

The scientists drew blood samples from people with HIV and exposed nonmodified HIV and the modified HIV to those samples. They found that HIV-specific antibodies neutralized the virus with the mutant Env that remained open but not the standard virus with the closed Env.

These findings confirm that most of the antibodies the immune system produces to counteract HIV are not able to pierce the closed Env structure, which is held together thanks to those two tyrosines. This further understanding of Envís complexities will hopefully aid in the quest to develop new vaccine candidates.
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