Biologists have understood what trick HIV uses to penetrate the cell nucleus
Scientists have made an important discovery for understanding how the human immunodeficiency virus enters the nucleus of a cell, allowing it to multiply and spread. To do this, they conducted computer simulations involving thousands of proteins, which looked at the HIV capsid (the capsule that contains the material of the virus) and the nuclear pore complex of the cell – the mailbox through which genetic information is sent and delivered.
“The pore complex is an incredible mechanism,” says Gregory, a theoretical chemist. This is from the University of Chicago. “It can’t let anything into the cell nucleus or you’ll have serious problems, but it has to let a lot of things through. The HIV capsid somehow figured out how to get inside. The problem is that we can’t observe it live: to get even one snapshot requires an incredible experimental effort.”
Modeling showed that the HIV capsid wedges into the cell first with the narrow end, and then with the help of a so-called electrostatic ratchet. Researchers compare it to a seat belt in a car that gets tighter and tighter.
Another key finding is that the flexibility and deformability of both the capsid and the pore play a critical role in capsid traversal. In order to withstand the additional pressure, the capsid forms regions of less ordered molecules, and the researchers believe that this may explain its cone-like shape.
Previously, researchers were sure that the capsid remains completely intact, that it squeezes through the time complex. A deeper understanding of what is happening will help in the study of cellular interactions.
“I think this simulation also gives us a new way to understand how many things get into the nucleus, not just HIV,” Osi said.