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article imageScientists successfully 'delete' HIV virus from human DNA

By Megan Hamilton     Mar 27, 2015 in Science
Over the decades, HIV has remained elusive, meaning a cure couldn't be found. A wizard at installing its genome into human DNA, it is impossible for our immune system to get rid of it.
Current treatments are effective at keeping the disease at bay, but in so doing, patients are subjected to a lifetime of toxic drugs.
Fortunately, that may be about to change.
Researchers at Temple University have possibly figured out a way to permanently exise it by using an HIV 'editor,' Endgadget reports. By analyzing the part of our immune system that's dedicated to fighting infection, the team built a "guide RNA" strand consisting of 20 nucleotides. These nucleotides are RNA building blocks. The strands were then injected into cells that are typically infected with HIV, such as T-cells. Once there, the strands targeted the end parts of the virus's gene pool, snipping out all 9,709 nucleotides that make up its genome. The guide RNA strands contained no human DNA sequences, therefore it left the host cell intact, but fortunately free from HIV.
This breakthrough marks the first successful effort to eliminate latent HIV- 1 virus from human cells,and it could also be a cure for other latent infections, the researchers said, Guff.com reports.
"This is one important step on the path toward a permanent cure for AIDS," Kamel Khalili, PhD, Professor and Chair of the Department of Neuroscience at Temple University said. "It's an exciting discovery, but it's not yet ready to go into the clinic. It's a proof of a concept that we're moving in the right direction."
More than one million people in the U.S. have HIV, out of a total of 33 million worldwide. Each year, an additional 50,000 Americans contract the virus, the Centers for Disease Control and Prevention reports. Around 100,000 people were living with HIV in the UK in 2013. Antiretroviral therapy has controlled HIV- 1 for those infected in the developed world for the last 15 years, but the disease can be exacerbated if treatment is interrupted, Guff.com reports.
There's other promising news on the HIV front as well.
Researchers at Yale University have identified a type of combined immunotherapy that enhances the body's ability to fight chronic viral infections, and possibly cancer, Science Daily reports.
Viruses that cause chronic infections like HIV and Hepatitis B and C, can easily persist in the body despite attack from T-Cells, the body's main warriors against pathogens. These viruses persist because they weaken our T-cells over time, to the point of "T-cell exhaustion." So the research team circumvented the problem by investigating two pathways that cause T-cell suppression.
The first pathway is triggered by the prostaglandin E2 (PGE2), a lipid that suppresses the immune system's response to tumors. In order to explore the relationship between PGE2 and T-cells, the team, led by Susan Kaech, an associate professor of immunobiology at Yale School of Medicine, studied mice with viral infections and found that PGE2 levels increased, especially during chronic infection. The enhanced PGE2 reduced the number of T-cells that attack the infected cells and also reduced the T-cells' anti-viral functions, Science Daily reports.
T-cells have receptors that keep them in balance by telling them to stop or go.
"What we have discovered is that PGE2 is another type of receptor giving a stop signal," Kaech, who is also a member of the Yale Cancer Center, said. When Kaech's team studied mice without PGE2 receptors, or without the ability to synthesize normal amounts of PGE2, the T-cells thrived.
Then the scientists tested the combined effect of systemically reducing PGE2 while also PD-1 (another pathway). Previous studies showed that PD-1 inhibited T-cells. The researchers treated virus-infected mice that lacked normal PGE2 production with anti-PD-1 antibodies, and found that the combined blockade of PGE2 and PD-1 vastly increased T-cell function and improved viral control.
"Blocking both pathways leads to an augmentation of the antiviral response that is bigger than either treatment alone," Kaech said.
In the final step, the researchers discovered they could achieve the same boost to T-cells by administering celecoxib (Celebrex), a non-steroidal anti-inflammatory drug (NSAID) that is used for pain management.
"Since these inhibitors are already in common use, we wondered if using them to decrease PGE2 signaling would also improve T-cell responses," Jonathan Chen, the first author on the study said. He is also a resident in pathology at Massachusetts General Hospital.
What's the most important take-away from this?
There's the potential of usings NSAIDs as a form of adjunct therapy for patients with chronic infections and cancer, Science Daily reports.
"By administering a medicine many of us take routinely, we could potentially augment the effects of PD-1 blockade, which is showing remarkable outcomes in cancer trials," said Kaech.
So, with the results of these studies, the future is looking better for HIV patients.
More about scientists delete hiv, HIV, Human dna, current treatments, Temple university
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