Gladstone has made significant contributions to fighting HIV/AIDS, paving the way for many medications currently in use and leading to a global and groundbreaking effort in HIV prevention.

Today, antiretroviral drugs can help prolong lifespan and improve the quality of life for people with HIV. However, patients require lifelong treatment with daily medications because the virus persists in a latent form. Researchers in the Gladstone Institute of Virology continue to explore the biological basis for HIV latency, which represents the greatest barrier to a cure.

The institute has also expanded its focus to study other viruses and infectious diseases, and look for unique strategies to treat multiple viruses at once. Gladstone scientists are searching for new biological targets for drugs that will attack the hepatitis C virus, which affects 170 million people worldwide. They are also investigating how viruses like Zika interact with cells in the mammalian brain to understand how they cause disease and how to intervene in that process. Additional studies have revealed transcriptional circuits in herpes viruses, such as cytomegalovirus and herpes simplex viruses, which control how the viruses replicate once they infect a cell.

In addition, our researchers are working to counter the growing resistance to antibiotics and antiviral drugs. One approach consists of focusing on human host proteins to prevent or treat viral and infectious diseases, while another entails hijacking a virus’s control circuitry to turn the biology against itself.

Gladstone scientists also train the future generation of scientists interested in virology and immunology. Learn more about Gladstone’s training programs.

“Our goal is to discover the most impactful disease mechanisms and translate basic scientific discoveries into better treatments for patients.”

Melanie Ott, MD, PhD
Director, Gladstone Institute of Virology

Major Scientific Achievements

Led the Global iPrEx Study for HIV Prevention

A Gladstone team demonstrated for the first time how two antiretroviral drugs, combined in a single tablet, can be used to prevent HIV infection in high-risk populations, providing proof of concept for pre-exposure prophylaxis. Because of this study, the World Health Organization and the Centers for Disease Control and Prevention now include this approach in their guidelines for physicians as part of a comprehensive prevention plan.

Discovered How HIV Hedges Its Bets to Increase Its Chances for Successful Infection

HIV covers its bases by generating both active and dormant infections. The active state allows the virus to spread and infect more cells, whereas virus in the latent state can survive in hiding for long periods of time. While the active virus can be killed by antiviral drugs, the latent virus cannot be treated by current therapies and represents the main obstacle to curing HIV. Gladstone researchers uncovered how HIV makes a decision and finally commits to one fate after randomly switching between the active and latent states. Their study demonstrates that HIV conserved a highly inefficient process on purpose, and by correcting it, scientists could significantly harm the virus. These findings could reveal unexplored targets for the development of novel HIV cure strategies.

Revealed a New Method to Address a Major Barrier to Eradicating HIV

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. A group of scientists at Gladstone discovered that an enzyme called SMYD2 can be inhibited to reactivate, or wake up, latent cells. SMYD2 could therefore be a new therapeutic target for flushing out the HIV that hides in infected individuals. Their findings offer new biological and mechanistic insights into how HIV latency functions.

Uncovered a New Way to Attack Herpesviruses

Human cytomegalovirus, a leading cause of birth defects and transplant failures, bypasses the body’s defense mechanisms that usually guard against viral infections by carrying its DNA into the cell along with specific proteins. However, these proteins die within a few hours of entering the cell, while it takes days to create new virus. Gladstone scientists uncovered the mechanism that allows the virus to successfully replicate even after these proteins are gone. Their study could open new therapeutic avenues to attack cytomegalovirus and other herpesviruses.

Identified an Anti-Aging Protein That Could Rejuvenate Immune Cells

Gladstone researchers revealed that a protein called SIRT1, commonly known for being activated by a component of red wine, could also be targeted to rejuvenate cells in the immune system. After identifying the crucial role played by SIRT1 in the aging of immune cells, they identified two potential new treatment targets. First, new drugs could be developed to strengthen SIRT1, which could postpone the development of age-related diseases and help people with a weaker immune system fight infections or better respond to immune vaccination. Second, drugs could be used to obtain the opposite effect on SIRT1 to support an aggressive anti-tumor response or other immune therapeutic approaches.

Director’s Message