FEB 09, 2021 8:00 AM PST

Putting the Kibosh on HIV's Stealth Tactics

WRITTEN BY: Tara Fernandez

The human immunodeficiency virus or HIV is always one step of the immune system, a tactic that makes it impossible to completely eradicate without the use of drugs. The power of the virus over the immune cells lies in its ability to shapeshift, constantly mutating as a means of disguising itself and evading recognition.

Clinical countermeasures to fight back have come a long way over the past few decades; HIV-positive patients on a daily regimen of antiretroviral drugs usually have almost undetectable levels of active HIV in their systems. Keeping these levels low, however, is inextricably linked to faithfully taking the lifelong course of medication. Interruptions can cause the virus to resurface and lead to serious health complications.

A recent study published in Science explores an exciting new possibility: instead of merely keeping the virus at bay, there may be a way of eradicating it completely. Scientists at the Washington University School of Medicine took a closer look at the dynamics of the dormant virus lying in wait within human immune cells. As the virus mutates in a bid to stay out of sight, one thing remains constant—the activity of HIV protease, a protein critical for the replication and spread of the virus.

"When we identified a part of the immune system that could recognize and attack a core function of the HIV virus—rather than what it looks like—it was really exciting," said Liang Shan, a senior author of the publication. 

According to Shan, protease activity is easier to distinguish than genetic characteristics of the viruses. For example, wearing a disguise might conceal a criminal’s true identity, but running away from the scene of a crime is harder to conceal.

“This is exciting because it raises the possibility of clearing all the dormant virus in a single patient—no matter how widely mutated—based on something all the viral variants have in common,” explained Shan. “For patients, even if they are consistent with therapy and experience no symptoms, having a treatment that could change their HIV status from positive to negative would have a massive impact on their lives."

Shan and colleagues discovered that human immune cells have an in-built security system—the CARD8 inflammasome. This defense mechanism is triggered when HIV protease activity is detected, causing cells to push the self-destruct button and diminish the viral spread risk. However, the virus can lay low in a dormant state for decades without activating the inflammasome.

The team found a way of smoking out the virus when it is in hiding, using drugs that force the activation of HIV protease. Doing this also sets off the inflammasome which in turn activates apoptosis, a molecular cascade that ends with cell destruction, taking the virus down with it.

"HIV protease's specific action for the virus is also the specific action that sets off CARD8,” said Shan. “Our findings show that our immune system can recognize a virus's protein function and, under the right circumstances, use that information to kill HIV-infected cells."

Some of the drugs that activate HIV proteases are already in the clinic, such as a class of pharmaceuticals known as non-nucleoside reverse transcriptase inhibitors (NNRTIs). The team’s discovery points to the feasibility and potential of using such therapeutics to stamp out the virus from infected individuals once and for all.

"We would like to identify or develop compounds that do an even better job of activating HIV protease than NNRTIs do and at lower doses," said Shan. "This study serves as a guide for developing new drugs that have the potential to eliminate the dormant HIV reservoir."

 

 

Sources: Science, Washington University School of Medicine St. Louis.

About the Author
  • Tara Fernandez has a PhD in Cell Biology and has spent over a decade uncovering the molecular basis of diseases ranging from skin cancer to obesity and diabetes. She currently works on developing and marketing disruptive new technologies in the biotechnology industry. Her areas of interest include innovation in molecular diagnostics, cell therapies, and immunology. She actively participates in various science communication and public engagement initiatives to promote STEM in the community.
You May Also Like
OCT 19, 2021
Drug Discovery & Development
Researchers develop a potent antiviral drug for dengue fever
OCT 19, 2021
Researchers develop a potent antiviral drug for dengue fever
Dengue fever is a mosquito borne illness that is widespread, especially in tropical countries. The global incidence of d ...
NOV 05, 2021
Cancer
The Labroots 2021 Cancer Research and Oncology Virtual Event Poster Winner
NOV 05, 2021
The Labroots 2021 Cancer Research and Oncology Virtual Event Poster Winner
Every year, Labroots hosts an exciting series of Virtual Events that focus on various scientific topics. These virtual m ...
NOV 21, 2021
Microbiology
Rare Genetic Variant Can Make People Susceptible to Bird Flu H7N9
NOV 21, 2021
Rare Genetic Variant Can Make People Susceptible to Bird Flu H7N9
Zoonosis is a serious health concern, as the COVID-19 pandemic has shown. Viruses that infect one species can acquire ge ...
DEC 09, 2021
Cannabis Sciences
Considering Cannabinoids as a COVID-19 Treatment
DEC 09, 2021
Considering Cannabinoids as a COVID-19 Treatment
Research suggests that Cannabis sativa-derived cannabinoids – such as cannabidiol (CBD), Δ9tetrahydrocannabi ...
DEC 16, 2021
Health & Medicine
Could Stem Cells Cure Type 1 Diabetes?
DEC 16, 2021
Could Stem Cells Cure Type 1 Diabetes?
For people living with chronic diseases like Type 1 diabetes, the word "cure" sounds too good to be true. In f ...
JAN 18, 2022
Drug Discovery & Development
Identification of a protein involved in the mucus-producing process in severe asthma
JAN 18, 2022
Identification of a protein involved in the mucus-producing process in severe asthma
Asthma is a chronic condition that is characterized by difficulty breathing, coughing, and wheezing which is caused ...
Loading Comments...