An interdisciplinary team of researchers at the Indian Institute of Science (IISc) has used robust computer simulations to understand how HIV – the virus that causes AIDS – fuses with the host cell membrane.
It was published in the Journal of Chemical Information and Modeling, the study focuses on a process called gp41–mediated membrane fusion.
Gp41, a core component of the HIV envelope protein (Env), is essential for the viral membrane to fuse with the cell membrane of the host’s immune cell, called T cell. This step is critical for HIV to invade and subsequently replicate within the host cell.
Although a lot is known about the molecular details of viral entry, the optimal stoichiometry – the balance of components – required for infection has remained uncertain. “We wanted to see … how many gp41 units are required to achieve this process,” explains Prabal K Maiti, Professor and Chair of the Department of Physics and the corresponding author.
The HIV envelope protein assembles into a three-part structure such that each unit comprises one gp41 protein. At the time of fusion, gp41 appears to fold into a six-helix bundle structure, which is thought to be necessary for membrane fusion.
The researchers also analysed the nature of lipid transfer during fusion and found that the trio of gp41 units drives changes to the structure and arrangement of lipids at the site of fusion. Finally, using mathematical calculations, the team found that the presence of gp41 reduces the energy required for fusion by about four-fold, thereby making this process more favourable.