A collaborative effort between investigators at the Yerkes National Primate Research Centre, Emory University School of Medicine and Georgia Institute of Technology has led to the development of a non-invasive method to image simian immunodeficiency virus (SIV) replication in real-time, in vivo. This approach is based on immune positron-emission tomography/computed tomography (PET/CT) and allows for the capture of viral dynamics of SIV, the animal model of human HIV infection, reports Medical Xpress. This novel approach has broad application to the study of immunodeficiency virus pathogenesis and drug and vaccine development, as well as to the potential use with human patients to identify viral reservoirs potentially leading to a cure of HIV/Aids.
Dr Francois Villinger, a researcher in the Yerkes Research Centre's Microbiology and Immunology division, and Dr Philip Santangelo, a researcher at Emory University and in the Wallace H Coulter Department of Biomedical Engineering at Georgia Institute of Technology, spearheaded the study with their respective teams and collaborators at the Emory School of Medicine. Using the non-human primate model of human HIV infection, their approach uncovered novel, previously unappreciated sites of viral replication, such as in nasal-tissue and the reproductive organs.
In addition, the methodology was able to capture the previously unappreciated wide variation in viral replication levels within select organs, including sections of the gastrointestinal tract, whether or not the subject was taking antiretroviral therapy (ART). Finally, the methodology allows for repeat analysis of the viral dynamics, for example during acute infection, during ART and upon cessation of ART.
"Use of the technique could lead to a better understanding of viral dynamics in the body, which could help target new generations of therapeutics and diagnostics," said Santangelo. "This could help us find the regions where the virus is replicating and allow us to focus molecular diagnostics on the areas that are really important," he says.
Commenting on the research in Science Mag, Timothy Schacker of the University of Minnesota, Twin Cities, who studies how HIV causes disease, said: "The entire upper respiratory tract is rich with lymphatic tissue, and we just never thought of that. That’s a really cool finding."
"It's fantastic," says Thomas Hope, an immunologist at Northwestern University Feinberg School of Medicine in Chicago, Illinois, who investigates how HIV, the human counterpart to SIV, infects cells. "The whole monkey shows you things you can’t comprehend by just looking at cells or biopsies of tissues."
David Margolis, who has pioneered human studies that attempt to shock and kill reservoirs, says immunoPET is a "nice new tool" but cautions that it's unclear to him how well the signals it detects match viral levels in the body. He also notes that a great deal of latent HIV DNA codes for defective, "dead-end" viruses that cannot cause infection themselves. If the labelled antibodies detect their presence, it could be misleading when it comes to evaluating whether reservoirs are shrinking.
Hope agrees that immunoPET tracking of AIDS viruses needs to be refined and still has technical hurdles to clear, but says the work advances the field.
[link url="http://medicalxpress.com/news/2015-03-tool-visualizes-body-siv-replication.html"]Full Medical Xpress report[/link]
[link url="http://www.nature.com/nmeth/journal/vaop/ncurrent/full/nmeth.3320.htm"]Nature Methods abstract[/link]
[link url="http://news.sciencemag.org/biology/2015/03/live-look-aids-virus"]Full Science Mag report[/link]