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The Cutting Edge

Researchers Create Molecule that Could 'Kick and Kill' HIV

Current anti-AIDS drugs are highly effective at making HIV undetectable and allowing people with the virus to live longer, healthier lives. The treatments, a class of medications called antiretroviral therapy, also greatly reduce the chance of transmission from person to person. But the medications do not actually rid the body of the virus.

HIV has the ability to elude medications by lying dormant in cells called CD4+ T cells, which signal another type of T cell, the CD8, to destroy infected cells. When a person with HIV stops treatment, the virus emerges and replicates in the body, weakening the immune system and raising the likelihood of opportunistic infections or cancers that can sicken or kill the patient.

Researchers have been looking for ways to eliminate the “reservoirs” where the virus hides, and scientists from UCLA, Stanford University and the National Institutes of Health may have developed a solution. Their approach involves sending an agent to “wake up” the dormant virus, which causes it to begin replicating, so that either the immune system or the virus itself would kill the cell harboring HIV.

Scientists call the technique “kick and kill.”

Destroying the reservoir cells could rid some or all of the HIV virus from people who are infected. And although the scientists' approach has not yet been tested in humans, a synthetic molecule they developed has been effective at kicking and killing HIV in lab animals.

“The latent HIV reservoir is very stable and can reactivate virus replication if a patient stops taking antiretroviral drugs for any reason,” says Matthew Marsden, PhD, assistant professor of medicine in the Division of Hematology/Oncology. “Our study suggests that there may be means of activating latent virus in the body while the patient is on antiretroviral drugs to prevent the virus from spreading and that this may eliminate at least some of the latent reservoir.”

To test the approach, the researchers gave antiretroviral drugs to mice that had been infected with HIV and then administered a synthetic compound called SUW133 to activate the mice's dormant HIV. Up to 25 percent of the previously dormant cells that began expressing HIV died within 24 hours of activation. With further development, the technique could lower the viral reservoir enough for people with HIV to be able to discontinue their antiviral therapy, Dr. Marsden says.

SUW133 is based on bryostatin 1, a natural compound extracted from a marine animal called Bugula neritina. The research determined that the new compound is less toxic than the naturally occurring version. In further studies, the scientists plan to learn how to make SUW133 less toxic and to evaluate its effectiveness in larger animals before it could be tested in humans.

“In Vivo Activation of Latent HIV with a Synthetic Bryostatin Analog Effects Both Latent Cell ‘Kick’ and ‘Kill’ in Strategy for Virus Eradication,” PLOS Pathogens, September 21, 2017

Scientists have found they can spark the immune system or the virus itself to kill the cell harboring HIV

By sending an agent to “wake up” the dormant HIV virus, causing it to begin replicating, scientists have found they can spark the immune system or the virus itself to kill the cell harboring HIV.
Image: A. Harrison and Dr. P. Feorino/CDC


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Winter 2018

Winter 2018
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IN THIS ISSUE
  • Partners in Care
  • Mobile Stroke Unit: Hospital on Wheels
  • Sip Black Tea to Drop Pounds
  • As Re-hospitalizations Go Down, Mortality Goes Up
  • Modified Herpes Virus Shows Promise for Treating Advanced Melanoma
  • Weak Burst of Electricity Can Help to Improve Memory
  • Heart's Pumping Function Doesn't Indicate Heart Failure Survival Rates
  • Biomarkers Could Reveal Undetected Concussions
  • Researchers Create Molecule that Could 'Kick and Kill' HIV
  • Study Blames Mental Lapses on Sleep-deprived Brain Cells
  • Behavioral Therapy Increases Connectivity in Brains of People with OCD
  • New Direction in Hand Transplantation
  • UCLA Vine Street Clinic
  • Tailor Made
  • Ilana and the Stowaway
  • Heartfelt
  • Awards/Honors
  • In Memoriam
  • Department of Surgery Celebrates Inaugural Paul I. Terasaki Chair in Surgery
  • Out of Africa, Into Iraq
  • Rides, Games and Laughter on the Pier
  • UCLA Health System Board Meeting Features Stroke Care
  • UCLA Launches New Mobile Stroke Unit
  • UCLA Operation Mend Marks a 10-year Milestone
  • Celebrating 60 Years of Excellence in Cardiovascular Research
  • The Spectacular Sounds of Autism
  • Family’s Bravery Leads to Generosity
  • A Legacy for Loved Ones
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  • In Memoriam
  • ‘I Have Been on Both Sides’
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