Discovery of tricky protein structure to aid HIV vaccine advances

  • Three legs of the critical gp41 HIV protein are shown in yellow. Blue and red show where antibodies can bind and neutralize the virus when the legs are extended. Image credit: Patrick Reardon, Leonard Spicer
  • This illustration shows how the envelope proteins covering the surface of an HIV virion (1, 2) bind to a host cell (3, 4). The trimeric MPER region of gp41 is shown in red and can be disabled by antibodies, shown in light blue. Image credit: Marian Miller
Date:14 January 2014 Tags:, ,

Researchers at Duke University have determined the structure of a key part of the HIV envelope protein, the gp41 membrane proximal external region (MPER), which previously eluded detailed structural description.

The research will help focus HIV vaccine development efforts, which have tried for decades to slow the spread of a virus that currently infects more than 33 million people and has killed 30 million more.

The team reported the findings online in the early edition of Proceedings of the National Academy of Sciences.

The envelope protein complex is a structure that protrudes from HIV’s membrane and carries out the infection of healthy host cells. Scientists have long targeted this complex for vaccine development, specifically its three copies of a protein called gp41 and closely associated partner protein gp120.

“The attractiveness of this region is that, number one, it is relatively conserved,” said Leonard Spicer, senior author and a professor of biochemistry and radiology. In a virus as genetically variable as HIV, a successful vaccine must act on a region that will be conserved, or similar across subtypes of the virus.

“Second, this region has two particular sequences of amino acids that code for the binding of important broadly neutralising antibodies,” said Spicer. The HIV envelope region near the virus membrane is the spot where some of the most effective antibodies found in HIV patients bind and disable the virus.

The next steps of this research have already begun. In December, Duke University received a grant of up to $2,9 million (about R31,5 million) from the Bill & Melinda Gates Foundation to fund the development of an HIV vaccine that will build on these findings.

Source: Duke University