Frederick National Lab scientists have developed a faster, more accurate way of pinpointing minute pockets of the AIDS virus that can hide out in infected tissue, thus exposing these remnants as targets for more definitive treatment of the infection.

Current antiretroviral drug treatments targeting the AIDS-causing human immunodeficiency virus (HIV) can effectively suppress the infection in patients, blocking the ability of the virus to infect new target cells, but the drugs do not eliminate already infected cells. Consequently, the virus can persist at low, difficult-to-detect levels. If treatment is stopped, this small amount of persisting virus can give rise to a full-blown spreading infection, potentially leading to AIDS if not treated.

As a result, infected individuals must continue their daily drug treatment indefinitely to prevent recurrence of the disease. Finding ways to target and reduce or eliminate this persisting virus is a major objective in current research on HIV/AIDS, and developing better ways to measure the residual virus is an important step toward this goal.

The new technique for tracking HIV—and the related monkey virus, Simian Immunodeficiency Virus (SIV), which causes AIDS in macaque monkeys and is the most widely used animal model for HIV/AIDS studies—focuses on immune system cells in lymphoid tissues. While much AIDS-related research involves studies of peripheral blood, which is commonly used for analysis because it is easier to obtain from patients, AIDS is a disease of the lymphoid system. Thus, researchers have developed a new way of visually examining these tissues and conducting parallel studies of tissues from SIV-infected rhesus macaques and HIV-infected humans.

The scientists designed and used highly sensitive, next-generation molecular probes to detect genetic material from HIV and SIV in infected cell tissue examined under a microscope. Compared to previous methods, the new approach provides greater sensitivity and specificity for detecting very low levels of AIDS virus genetic material, allowing detection of even a single virus particle.

The new technique has also unlocked the ability to detect AIDS virus DNA and RNA in the same specimen, a key enabling capability for understanding the role that a dormant virus in latently infected cells plays in maintaining persisting virus, despite antiretroviral drug treatment. The new technique for detecting viral genetic material can also be combined with approaches to use antibodies to identify different types of cells, helping to determine which kinds of cells harbor the persisting virus.

“This allows us to see in greater detail than ever before where small amounts of virus lie in wait, providing insights into the mechanisms they use to persist, despite treatment,” said lead investigator Jacob Estes, Ph.D., of the AIDS and Cancer Virus Program, Frederick National Lab. Results of the study appear in the inaugural issue of the cutting-edge online journal, Pathogens and Immunity. Materials for replicating the work are being made available to the scientific community at large.

The research group included collaborators from the University of Minnesota and University of California, San Francisco.

Image: Representative low and high magnification RNAscope in situ hybridization images from a chronically SIV-infected rhesus macaque (RM) (top panel) and a SIV-negative RM (bottom panel) demonstrating the robust detection of SIV vRNA only SIV-infected, but not in SIV-negative lymphoid tissues. Scale bars = 50 µm.​

Last updated: July 25, 2016