Paper in Immunity showed that the MPER region of gp41 is hidden in viral membranes, but certain antibodies can expose it.
By coaxing the HIV-1 protein to reveal a hidden portion of its coat, scientists report that they have a new detailed picture of how broadly neutralizing antibodies (BNAbs) block HIV-1 infection.
The study focused on an HIV-1 surface protein called gp41. Specifically, the team looked at a portion of it known as the membrane proximal ectodomain region (MPER). This region, which lies at the base of HIV’s envelope protein, is consistent across different strains of the virus. In theory, that should make it an attractive target for immune system antibodies, the researchers note. The antibody response to it, however, is rather meager.
To determine why this is so, the Dana-Farber Cancer Institute team studied its structure using NMR, electron paramagnetic resonance, and surface plasmon resonance imaging techniques. They discovered that MPER is not only immersed in the viral membrane giving it refuge from immune system attack but it also has a hinge in the middle, which provides flexibility and helps it attach to T lymphocytes.
Despite this stealthiness, the researchers found that a BNAbs called 4E10 homes in on the hinge area and in so doing, pulls out key portions of MPER that had been buried inside the membrane. Then, 4E10 latches onto these newly exposed sections, forming a tighter bond with the virus and blunting its ability to fuse with the cell membrane, the first step in viral infection.
The research was performed by investigators at the Dana-Farber and Harvard Medical School. The paper was published in Immunity on January 10 in advance of the print publication.