Scientists said on Wednesday they have discovered a key clue to how HIV mutates to evade the immune system that could advance the search for new drugs and a vaccine.
Researchers at the Children’s Hospital Boston and Harvard University Medical School have shown that the virus, which has infected 40 million people worldwide, alters its shape and triggers changes that allow it to enter cells.
They obtained a three-dimensional image of a protein called gp120, part of HIV’s outer membrane or envelope, before it transforms and binds to so-called CD4 receptors on the cells it wants to infect.
“Knowing how gp120 changes shape is a new route to inhibiting HIV — by using compounds that inhibit the shape change,” Stephen Harrison, head of the research team, said.
A 'technical tour de force'
Peter Kwong, of the National Institutes of Health in Maryland, described the research as a “technical tour de force” because scientists have sought the structure of the gp120 protein before it binds to CD4 receptors for almost 20 years.
“In terms of vaccine design, the structure ... reveals the envelope at its potentially most vulnerable,” he said in a commentary.
Antiretroviral drugs can prolong the lives of AIDS sufferers but they are expensive and beyond the reach of millions of people in the developing world.
A vaccine is considered the Holy Grail in the battle against the AIDS epidemic but efforts to find one have been hampered by HIV’s ability to mutate.
“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,” Harrison explained in a statement.
Scientists had already deciphered the structure of the protein after it binds to the cell it wants to attack. The findings published in the science journal Nature provide information about how the molecule rearranges itself before it attacks.
“We can now compare the bound and unbound forms and try to understand whether there are any immunologic properties that differ and that might provide a route to new vaccine or drug strategies,” said Harrison.
The scientists uncovered the shape of the unbound protein by aiming an X-ray beam through a crystallized form of gp120 from a monkey virus similar to HIV.
