An interdisciplinary team of researchers at the Indian Institute of Science (IISc) has used computer simulations to understand how the human immunodeficiency virus (HIV) that causes AIDS fuses with the host cell membrane.
According to an IISc release, 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, the release explained.
"If gp41 fusion is blocked, then the whole invasion can be blocked there,” explained Biswajit Gorai, a former postdoc at IISc and first author of the study, indicating that understanding the membrane fusion process may help researchers in developing effective antiviral strategies.
The release elaborated that though a lot is known about the molecular details of viral entry, the balance of components required for infection has remained uncertain.
“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,” it said.
In another first, the team built models of HIV and host membranes with lipid compositions nearly identical to biological membranes, the release said.
Currently, the team is working on identifying mutations that can be introduced in gp41 to block the fusion step. They are also hoping to develop antibodies that can prevent infection.
