HIV replication mechanism discovered, could mean new treatment
Researchers have discovered how HIV replicates inside immune fighting cells in an unexpected finding.
The discovery that comes from scientists at University of Rochester Medical Center and Emory University is expected to lead to new therapies that stop the AIDS virus.
The scientists knew HIV hides in immune fighting cells called macrophages and uses a molecule inside those cells to replicate, but they weren't sure how the virus interacted with the very same cells that normally destroy foreign invaders.
What they discovered is HIV taps into another available molecule within macrophages, sidestepping a normal building block known as dNTP (deoxynucleoside triphosphate).
Researchers Baek Kim, Ph.D.at the University of Rochester Medical Center, in conjunction with Emory scientist Raymond F. Schinazi, Ph.D., D.Sc., director of the Laboratory of Biochemical Pharmacology at Emory’s Center for AIDS Research, discovered how HIV adapts by tapping into a more plentiful molecule inside macrophages.
“The (HIV) virus would normally just use dNTP, but it’s simply not available in great quantities in the macrophage. So HIV begins to use rNTP, which is quite similar from a chemical perspective. This is a surprise,” said Kim. “The virus just wants to finish replicating, and it will utilize any resource it can to do so.”
The findings mean there is another way to stop HIV replication within macrophages. Current drugs target dNTP, not rNTP in CD4+ T. immune cells.
“The first cells that HIV infects in the genital tract are non-dividing target cell types such as macrophages and resting T cells” said Kim. “Current drugs were developed to be effective only when the infection has already moved beyond these cells. Perhaps we can use this information to help create a microbicide to stop the virus or limit its activity much earlier.”
Kim notes Cordycepin, derived from wild mushrooms and in development as an anti-cancer drug targets rNTP. The research team plans to test the same type of compounds to see if they can stop HIV replication, given the new findings.
Schinazi who developed some of the current drugs used for HIV treatment says, “This significant breakthrough was unappreciated prior to our paper. We are now exploiting new anti-HIV drugs jointly based on this novel approach that are essentially not toxic and that can be used to treat and prevent HIV infections.”
The researchers have been trying to understand how HIV hides in the body, surviving for decades, something that has fascinated Kim for 15 years. When the team blocked the ability of HIV to interact with rNTP, replication of the AIDS virus was reduced 90 percent.
The discovery should lead to non-toxic drugs that stop HIV from replicating, offering an entirely new approach for preventing the disease and for treating patients infected with the AIDS virus.
J. Biol. Chem. 2008 283: 9206-9216: doi:10.1074/jbc.M710149200