HIV’s trick to invade the host cell nucleus: ScienceAlert
Scientists have made an important discovery in understanding how HIV – commonly known as HIV – penetrates the cell nucleus, enabling it to replicate and spread.
This process has been somewhat mysterious until now, and the research team from the University of Chicago say their findings will help understand HIV and its effect on the body. Ultimately, it could lead to better treatments.
To find out exactly how HIV invades the cell nucleus, simulations were performed involving thousands of proteins, looking at the HIV capsid (the capsule that contains the virus material) and the cell’s nuclear pore complex; The mailbox slot through which genetic information is sent and delivered.
“The pore complex is an amazing piece of machinery,” says theoretical chemist Gregory Voth of the University of Chicago. “It can’t let anything into the nucleus of your cell, otherwise you’ll be in real trouble, but it has to let a whole lot of stuff in. Somehow, the HIV capsid has figured out how to sneak in.”
“The problem is that we can’t watch it live: you have to put in heroic experimental efforts to get one shot at the right time.”
Simulations revealed that the HIV capsule gets stuck in the smaller limbs first, before what is known as an electrostatic ratchet is applied. Researchers compare it to a car seat belt, as it becomes tighter.
Another key finding is that flexibility and deformability of both the capsid and the pore are crucial in allowing the capsid to pass through. The capsid develops regions of less-ordered molecules in order to accommodate the additional pressure, and researchers believe this may explain its conical shape.
Previously, researchers were not sure whether the capsid remained completely intact as it squeezed through the pore complex. Getting a better view of what’s going on here will help study cell interactions in general.
“I think this modeling also gives us a new way of understanding how many things get into the nucleus, not just HIV,” Voth says.
This is just one of many steps in the infection process, although it is essential to the way HIV infection maintains itself in its host’s body. Being able to stop this would be an important step forward in finding a complete cure for the virus.
Any treatment that somehow interrupts this deceptive escalation method would harm HIV’s chances of survival, and the researchers point out that there are likely a number of ways to do this.
“For example, you could try to make the HIV capsid less flexible, which our data suggest would hinder its ability to enter the nucleus,” says chemist Arba Hidayat of the University of Chicago.
The research was published in With people.