Federal funds may help Gladstone to solve problem of HIV latency

Participation in Martin Delaney Collaboratory increases hope of resolving HIV latency

The Gladstone Institutes will receive funds totaling $5.6 million over five years as part of the first-ever major funding initiative focusing on HIV eradication. The funds will help three principal investigators at Gladstone, an independent biomedical-research organization, to explore the molecular basis for HIV latency where the virus that causes AIDS "hides" dormant within cells waiting for an opportunity to reemerge when therapy is withdrawn.

"A critical factor to finding a cure for AIDS is to solve the problem of HIV latency," said Warner Greene, MD, PhD who leads all virology and immunology research at Gladstone. "If we can inhibit latency, then a cure for HIV-infected patients could be within our reach."

AIDS has killed more than 25 million people around the world since first being identified some 30 years ago. In the United States alone, more than one million people live with HIV/AIDS at an annual cost of $34 billion. Patients require lifelong treatment for AIDS because the HIV virus persists in a dormant and drug-insensitive form. Better understanding this latency, and developing new ways to attack it, could finally make it possible to cure HIV-infected patients.

The funding to cure this latency is part of the Martin Delaney Collaboratory - a consortium among academia, government and private industry that the National Institutes of Health is funding and that Dr. Greene helped create. The National Institute of Mental Health also provided co-funding.

With these funds, Dr. Greene's laboratory will seek to identify previously unrecognized products in the cell that help maintain HIV latency - ultimately working to develop inhibitors against these cellular proteins. Dr. Greene's laboratory also will analyze the action and targets of various regulatory molecules known as microRNAs that are present in latently infected CD4 T cells. Eric Verdin, MD, will study the potential role of the cell's chromatin-remodeling machines in the establishment and maintenance of HIV latency; while Melanie Ott, PhD, will examine the role of histone methylation in HIV latency and the effects of small-molecule inhibitors that block the action of various methyl transferases.

"If we can successfully eradicate latency, we might be able to avoid drug therapy altogether," said Dr. Verdin, who is a senior investigator at Gladstone.

At the same time, Dr. Greene warned, any eventual cures or functional cures can't begin to end the global AIDS epidemic unless they can be effectively used in those places where the virus is most rampant - such as sub-Saharan Africa, where about two-thirds of all people afflicted with HIV/AIDS live.

"We must construct a therapy that is usable in both the developing and developed world," said Dr. Greene, who is also a professor of medicine, microbiology and immunology at the University of California, San Francisco (UCSF).