Synthetic molecule 'kicks and kills' some persistent HIV in mice

September 21, 2017, Public Library of Science
A) Structure of bryostatin 1. B) Structure of bryostatin analog SUW133. Credit: Marsden MD, et al. (2017)

Scientists have designed a synthetic molecule that can reactivate dormant human immunodeficiency virus (HIV) in mice and lead to the death of some of the infected cells, according to a study published in PLOS Pathogens.

The new findings address a long-standing challenge in HIV treatment: While antiretroviral therapy can successfully stave off disease progression, the virus can silently persist in some cells for many years, so an infected person must be vigilantly treated for the rest of their life.

Previous studies have explored potential ways to eliminate latently infected cells, such as by stimulating them to produce some viral particles ("kick"), followed by cell death via the immune system or the virus itself ("kill"). A molecule called bryostatin 1 holds the potential to trigger a "kick and kill" response, but it is costly to obtain from its source, a marine animal known as Bugula neritina.

To address this challenge, Matthew Marsden and Jerome Zack of UCLA and Wender Group colleagues at Stanford have designed synthetic molecules capable of imitating the activity of bryostatin 1 and perhaps even improving on its function. In the new study, the team tested SUW133, one of their more promising synthetic bryostatin 1 analogs.

The researchers first demonstrated that SUW133, like bryostatin 1, is capable of activating latent HIV infection in cells removed from infected patients. Then, they tested SUW133 in mice of a strain commonly used for HIV research, in which the mouse immune system is modified to be similar to that of humans.

Molecular analysis revealed that SUW133 stimulated HIV protein production in latently infected cells in the mice. Within 24 hours, up to 25% of these cells then died. SUW133 was also better tolerated by the mice than was bryostatin 1.

These results support the potential for SUW133 to be used in a "kick and kill" treatment for HIV. Further research is needed to explore this potential and answer questions such as whether a greater percentage of cells could be killed over longer periods of time or with repeated dosing, whether similar effects might be seen in humans, and what the long-term effects of SUW133 may be.

Explore further: Kicking latent HIV: New strategies to reactivate reservoirs of latent infection

More information: Marsden MD, Loy BA, Wu X, Ramirez CM, Schrier AJ, Murray D, et al. (2017) In vivo activation of latent HIV with a synthetic bryostatin analog effects both latent cell "kick" and "kill" in strategy for virus eradication. PLoS Pathog 13(9): e1006575. doi.org/10.1371/journal.ppat.1006575

Related Stories

Kicking latent HIV: New strategies to reactivate reservoirs of latent infection

July 30, 2015
In cells with latent HIV infection, the virus is dormant, and such cells are therefore not attacked by the immune system or by standard antiretroviral therapy. To eradicate the virus from the human body and truly cure a patient, ...

Study observes potential breakthrough in treatment of HIV

June 17, 2016
A new study conducted by researchers at the San Francisco VA Medical Center (SFVAMC) observes that pharmacological enhancement of the immune systems of HIV patients could help eliminate infected cells, providing an important ...

Immune cells promote or prevent cytomegalovirus activity in mice depending on location

August 10, 2017
Immune system cells called regulatory T cells appear to promote cytomegalovirus (CMV) latency in the spleen of mice, but suppress it in the salivary gland. Maha Almanan of the University of Cincinnati College of Medicine, ...

Synthesized compound flushes out latent HIV

July 17, 2012
(Medical Xpress) -- A new collection of compounds, called "bryologs" – derived from a tiny marine organism – activate hidden reservoirs of the virus that currently make the disease nearly impossible to eradicate.

A viral protein that helps EBV-infected B cells to escape human killer T cells

June 11, 2015
About 90% of adults worldwide are infected with Epstein-Barr virus, or EBV. The virus infects B cells (the white blood cells that make antibodies) and can contribute to B-cell-derived cancers, but in most people it remains ...

Mouse model could shed new light on immune system response to Zika virus

February 23, 2017
A new mouse model with a working immune system could be used in laboratory research to improve understanding of Zika virus infection and aid development of new treatments, according to a study published in PLOS Pathogens.

Recommended for you

Deadly Rift Valley fever: New insight, and hope for the future

July 19, 2018
Health control measures alone could be ineffective in the long term fight against the deadly Rift Valley fever which affects both humans and animals, a new study in the journal PNAS reports.

New guidelines to diagnose, manage rare endocrine disorders

July 19, 2018
International guidelines have been published for the first time to help doctors around the globe diagnose and manage patients with a very rare set of endocrine diseases known as pseudohypoparathyroidism and its related disorders, ...

Overuse of antibiotics not what the doctor ordered

July 19, 2018
With increased use of antibiotics worldwide linked to growing antibiotic resistance, a world-first study co-authored by a QUT researcher has highlighted the growing impact of non-prescription supply of antibiotics in community ...

Alcohol-related cirrhosis deaths skyrocket in young adults

July 18, 2018
Deaths from cirrhosis rose in all but one state between 1999-2016, with increases seen most often among young adults, a new study shows.

Hidden blood in feces may signal deadly conditions

July 17, 2018
(HealthDay)—Even if it's not visible to the naked eye, blood in the stool can be serious—a sign of a potentially fatal disease other than colon cancer, new research suggests.

Childhood abuse linked to greater risk of endometriosis, study finds

July 17, 2018
Endometriosis, a painful condition that affects one in 10 reproductive-age women in the U.S., has been linked to childhood physical and sexual abuse, according to findings published today in the journal Human Reproduction.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.