Scientists at the Frederick National Laboratory for Cancer Research 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 do not eliminate already infected cells. Consequently, the virus can persist at low, difficult-to-detect levels and 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. So 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 development of better ways to measure the residual virus is an important task to enable this goal.
The new technique for tracking HIV (and the related monkey virus, Simian Immunodeficiency Virus, SIV, which causes an 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 so the researchers developed a new way of visually examining these tissues, conducting parallel studies of tissues from SIV-infected rhesus macaques and HIV infected humans.
The research group designed and used highly sensitive next generation molecular probes, to detect genetic material of HIV and SIV in infected cells in tissues examined under the 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.
Another advance provided by the new technique is the ability to detect AIDS virus DNA and RNA in the same specimen, a key enabling capability for understanding the role of dormant virus in latently infected cells 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 corresponding author Jacob Estes, Ph.D., of the AIDS and Cancer Virus Program, Frederick National Lab. Results of the study - which included scientists from the University of Minnesota, University of California, San Francisco - 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 Frederick National Laboratory for Cancer Research is a federal national laboratory sponsored by the National Cancer Institute and operated by Leidos Biomedical Research, Inc. Other support for the research came from the Delaney AIDS Research Enterprise funded by the National Institute of Allergy and Infectious Diseases.
This work was supported with federal funds from the National Cancer Institute (NIH Contract HHSN261200800001E), the Delaney AIDS Research Enterprise (DARE, U19AI096109), and R01 AI093319. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.
Article: Defining HIV and SIV Reservoirs in Lymphoid Tissues, Claire Deleage, Stephen W. Wietgrefe, Gregory Del Prete, David R. Morcock, Xing-Pei Hao, Jodi L. Anderson, Katherine Perkey, Michael Piatak, Jr., Julian Bess, Cavan Reilly, Joseph M. McCune, Ashley T. Haase, Jeffrey D. Lifson, Timothy W. Schacker, Jacob D. Estes, Pathogens and Immunity, > Vol 1, No 1 (2016).