US researchers have discovered a protein that appears to play a key role in helping HIV multiply in human immune cells.
The protein, called p32, may one day provide a potential target for drugs that keep HIV dormant and harmless.
This could eventually lead to what could essentially be a cure for HIV.
“P32 is part of the puzzle,” said Dr. Susanna Valiente, UF Scripps Professor of Innovation and Biomedical Technology and Chair of its Department of Immunology and Microbiology at the Herbert Wertheim UF Scripps Institute.
“This adds another layer of complexity to understanding HIV,” said Valente, lead author of the paper published in the Proceedings of the National Academy of Sciences. “We need to identify all of these unknown factors that help HIV replicate itself.” Finally, some of them could be targeted in the future with drugs.”
When HIV infects an immune cell, it can lie dormant for years. If not treated, viral loads eventually overload and weaken the immune system to the point that it can no longer ward off infection and disease. This final stage is AIDS.
Antiretroviral therapy, or ART, can lower HIV loads so that the patient does not develop AIDS. But this requires a daily regimen of medication that will last a lifetime. However, HIV still lingers in cells and causes low-level inflammation. This can put HIV-positive patients at greater risk for cardiovascular, kidney, bone or liver disease as well as for diabetes, cognitive disorders and some types of cancer, even when AIDS does not develop.
ART is not a cure for HIV but it allows to control it as a chronic disease. However, if treatment is discontinued, viral loads will rise again to dangerous levels.
Some HIV researchers have focused on a “shock and kill” strategy to eradicate the virus, bypassing antiretroviral therapy. This involves using drugs to awaken dormant HIV-infected cells, where they were invisible to the immune system.
Once activated, the immune system can attack and destroy virus-carrying cells.
However, Valiente said that goal remains a long way off, because it has proven difficult to reawaken and destroy every copy of the virus in the body without serious side effects. All it takes is one HIV-infected cell for it to spread again.
Instead, Valente devised an “occupational therapy” strategy called “block and lock.” It is a method that prevents HIV from reactivating in dormant cells without eliminating them, and then trapping them in that state.
This is where another important protein, the Trans-Activator of Transcription (Tat), plays a role. It is a regulatory protein that can promote the cellular assembly line that replicates the virus so that it can, in turn, spread and infect additional cells. Eliminating Tat could lock HIV into a permanent dormant state, Valiente says.
“Without Tat, you have a very weak virus,” she said.
p32 also interacts with Tat, helping to stabilize it, Valente said.
“Block-and-lock does not eliminate HIV. The virus is still there. We just put it to sleep like the harmless endogenous retroviruses that make up 8% of our genome,” the researcher explained.
“I’m optimistic that we can get a functional cure with this silencing approach,” she said, adding, “This new paper is not the cure for HIV. We’re not there yet. But every little step brings us closer” to a cure.
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