Study reveals a new method to address a major barrier to eradicating HIV

May 10, 2017, Gladstone Institutes
HIV infecting a human cell. Credit: NIH

Scientists at the Gladstone Institutes discovered that an enzyme called SMYD2 could be a new therapeutic target for flushing out the HIV that hides in infected individuals. Overcoming this latent virus remains the most significant obstacle to a cure.

While drug therapy allows people living with HIV to lead a relatively normal life, it also comes with adverse effects. In addition, patients must stay on the drugs for life to prevent the hiding in their body from reactivating. In the early stages of infection, HIV hides in viral reservoirs in a type of immune cells called T cells. This dormant, or latent, virus can then spontaneously reactivate and rekindle infection if is stopped.

To eliminate HIV latency, scientists are exploring a "shock and kill" strategy that would use a combination of drugs to wake up the dormant virus, then act with the body's own immune system to eliminate the virus and kill infected cells. Previous research has had limited success in efficiently reactivating latent HIV, so scientists are working to find new, more effective drugs.

"Our study focused on a class of enzymes called methyltransferases, which have emerged as key regulators of HIV latency," explained Melanie Ott, MD, PhD, a senior investigator at Gladstone and lead author of the study published in the scientific journal Cell Host & Microbe. "These enzymes have also become increasingly important in disease development, particularly cancer, and efforts have intensified to develop specific pharmacological inhibitors targeting them."

"We systematically screened over 50 methyltransferases to determine which ones regulate latency in infected T cells," said Daniela Boehm, postdoctoral scholar in the Ott lab and first author of the study. "We identified SMYD2 as a regulating enzyme, and found that inhibiting it reactivates, or wakes up, latent cells. SMYD2 could therefore be used as a therapeutic target in the shock and kill strategy."

Although SMYD2 was not previously considered a target for HIV, pharmacological inhibitors are already being developed against this enzyme due to its effect on various cancer tumors.

"Our findings offer new biological and mechanistic insights into how latency functions," added Ott, who is also a professor in the Department of Medicine at the University of California, San Francisco (UCSF). "They also suggest potential translational applications. Through a valuable collaboration with our industry partners, we obtained samples of small molecules in pre-clinical development that target SMYD2 and could potentially activate latent HIV."

In collaboration with Warner Greene, MD, PhD, the researchers tested the small molecules that inhibit SMYD2 in human cells.

"We found that these small SMYD2 inhibitors were able to activate the virus in latently infected T isolated from HIV patients," said Greene, senior investigator and director of the Gladstone Institute of Virology and Immunology.

"Our findings provide the basis for a new model of HIV latency wherein SMYD2 contributes to durably repressing the latent virus," said Ott. "They also underscore the emerging ties between cancer and HIV treatment through shared pharmacological targets. Though we are still far from a human application, it is exciting to know that data from this study might readily connect with clinical efforts."

Explore further: Study observes potential breakthrough in treatment of HIV

Related Stories

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 ...

Scientists advance understanding of herpesvirus infection

April 12, 2017
Herpes simplex virus (HSV) infections last a lifetime. Once a person has been infected, the virus can remain dormant (latent) for years before periodically reactivating to cause recurrent disease. This poorly understood cycle ...

Sugar-binding protein galectin-9 found to be a new weapon to cure HIV

July 13, 2016
The ultimate impediment to a cure for HIV infection is the presence of latent, HIV-infected cells, which can reawaken and produce new virus when antiretroviral drug therapy is stopped. These latent, HIV-infected cells are ...

Identification of drug combinations that reverse HIV-1 latency

March 30, 2015
There are almost 40 million people throughout the world living with HIV-1/AIDs. While current antiretroviral therapies are able to reduce the amount of virus in the blood, HIV remains present in a latent state within T cells. ...

Scientists zoom in on AIDS virus hideout

March 15, 2017
French scientists said Wednesday they had found a way to pinpoint elusive white blood cells which provide a hideout for the AIDS virus in people taking anti-HIV drugs.

New model to study HIV latency in brain cells

June 18, 2015
Over 35 million people worldwide are currently infected by HIV. Antiviral therapies can keep the virus from multiplying. However, no drug can cure infection so far, because various cell types continue to carry the virus in ...

Recommended for you

HIV exports viral protein in cellular packages

February 15, 2018
HIV may be able to affect cells it can't directly infect by packaging a key protein within the host's cellular mail and sending it out into the body, according to a new study out of a University of North Carolina Lineberger ...

Can gene therapy be harnessed to fight the AIDS virus?

February 13, 2018
For more than a decade, the strongest AIDS drugs could not fully control Matt Chappell's HIV infection. Now his body controls it by itself, and researchers are trying to perfect the gene editing that made this possible.

Big data methods applied to the fitness landscape of the HIV envelope protein

February 7, 2018
Despite significant advances in medicine, there is still no effective vaccine for the human immunodeficiency virus (HIV), although recent hope has emerged through the discovery of antibodies capable of neutralizing diverse ...

Scientists report big improvements in HIV vaccine production

February 5, 2018
Research on HIV over the past decade has led to many promising ideas for vaccines to prevent infection by the AIDS virus, but very few candidate vaccines have been tested in clinical trials. One reason for this is the technical ...

Microbiome research refines HIV risk for women

January 25, 2018
Drawing from data collected for years by AIDS researchers in six African nations, scientists have pinpointed seven bacterial species whose presence in high concentrations may significantly increase the risk of HIV infection ...

Researchers find latent HIV reservoirs inherently resistant to elimination by CD8+ T-cells

January 22, 2018
The latest "kick-and-kill" research to eliminate the HIV virus uncovered a potential obstacle in finding a cure. A recent study by researchers at the George Washington University (GW) found that latent HIV reservoirs show ...

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.