Research to Provide Deeper Understanding of Processes That Lead to Latency, Which Will Be Critical for Developing Curative HIV Therapies
The National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, has awarded a grant to researchers at New York University College of Dentistry (NYU Dentistry) to study HIV latency. The grant (R01AI145753), which began February 1, provides nearly $2 million over five years to support research led by David N. Levy, PhD, associate professor of basic science and craniofacial biology at NYU Dentistry.
HIV latency—in which the virus lies dormant in T cells—presents a troublesome barrier to developing treatments that eliminate HIV from the body. It is largely the result of repressive epigenetic changes to the HIV-associated chromatin, the substance within a chromosome consisting of DNA and protein. Understanding the epigenetic changes that result in productive infection versus latency would provide an important clue for developing a curative treatment.
“The search for treatments which might cure HIV infection or permanently repress the virus depend upon a thorough understanding of these processes,” said Levy. “Our research seeks to develop new knowledge on of the regulation of HIV-1 chromatin, the installation of nucleosomes, and their histone post translational modifications.”
The NIH-funded project will describe both the initial steps in HIV chromatization and the long-term processes that lead to reversible latency and irreversible repression. The researchers are investigating the earliest events in the establishment of HIV-1 chromatin organization, which they have determined occurs soon after reverse transcription and is influenced by both cellular and viral factors.
The research will also explore the influence of the viral protein Vpr on these processes. Previous research by Levy found that HIV-1 Vpr can reactivate latent HIV, and his new work demonstrates that Vpr influences the structure of HIV-1 chromatin that drives the switch between active replication and latency.
By defining the epigenetic landscape of newly generated HIV-1 genomes and latent proviruses, and the contribution of Vpr to this process, the researchers anticipate gaining useful insights into HIV infection and latency.
“These studies will provide vital information and perhaps new targets for the development of therapeutics that can purge HIV from the body or permanently repress virus replication without continual antiviral treatments,” said Levy.
"The recent announcement that a second person has been cured of HIV infection brings renewed optimism that a cure can be found that is more generally applicable. The two individuals who have been cured were also treated for cancer with bone marrow transplants, something that is not going to be useful to the HIV infected population at large. Nevertheless, achievements such as these provide vital clues about how to develop broadly useful methods for HIV clearance," Levy added.
About NYU College of Dentistry
Founded in 1865, New York University College of Dentistry (NYU Dentistry) is the third oldest and the largest dental school in the US, educating 9 percent of the nation’s dentists. NYU Dentistry has a significant global reach with a highly diverse student body. Visit http://dental.nyu.edu for more.