Scientists reveal key clue to how HIV infects cells

Harvard researchers have shown for the first time the critical “before” structure of an AIDS virus protein that plays a key role in the virus’ infection of cells.
The protein, called gp120, is responsible for binding to target immune system cells. Once the protein binds to the cell, it changes its shape, allowing a second protein to fuse with the cell membrane and permitting infection to occur.

Once inside the cell, the AIDS virus, also known as HIV, or the human immunodeficiency virus, takes over the cell’s own DNA and converts it to the job of making new viruses, which bud from the cell surface and spread the infection.

Though gp120’s structure after it changes shape was described several years ago, structural biologists at Children’s Hospital Boston and Harvard Medical School devised a way to view the structure before the shape change. That development, published in the Feb. 24 issue of the journal Nature, provides a vital reference point for researchers seeking ways to stop HIV from entering the cell.

The research team was led by Howard Hughes Medical Institute Investigator Stephen Harrison, a professor of biological chemistry and molecular pharmacology and professor of pediatrics, and Instructor in Pediatrics Bing Chen.

“Knowing how gp120 changes shape is a new route to inhibiting HIV – by using compounds that inhibit the shape change,” said Harrison. “The findings also will help us understand why it’s so hard to make an HIV vaccine, and will help us start strategizing about new approaches to vaccine development.”

The studies, performed in the Children’s Hospital Boston Laboratory of Molecular Medicine, used the closely related simian immunodeficiency virus (SIV) as a stand-in for HIV. By aiming an X-ray beam through a crystallized form of gp120, they obtained the first high-resolution three-dimensional images of the protein in its unbound form.