A new, noninvasive technique has been used to create a real-time map of the simian AIDS virus (SIV) in the entire body of a living monkey, researchers report today. The method is called immunoPET, and it's already turning up unexpected "viral reservoirs" where AIDS may gain a purchase in the body.
Borrowing a labeling strategy used in PET scans, a new imaging technique allows for real-time imaging of the AIDS virus (readily visible in yellow, in the image on the left), in a living being. The image on the right illustrates how the infection was attenuated following antiretroviral therapy. Image via Santangelo et al.
In an interview with Science News, Thomas Hope – an immunologist at Northwestern University who investigates how HIV infects cells and was unaffiliated with the development of immunoPET – called the novel technique "groundbreaking":
"It's fantastic," says Hope. "The whole monkey shows you things you can't comprehend by just looking at cells or biopsies of tissues."
To obtain this unprecedented look at an AIDS virus in action, a research team led by Francois Villinger of Emory University in Atlanta borrowed a technique used with cancer patients. The researchers began by attaching a radioactive molecule to an antibody that targets the surface protein of SIV. They then gave 12 monkeys chronically infected with SIV the harmless, engineered antibody, which sought out and latched onto the SIV in their bodies. A positron emission tomography (PET) scan detected the antibodies and thus revealed exactly where the virus was hanging out inside the monkeys. As expected from previous biopsy studies, the "immunoPET" scan indicated that the gut and lymph nodes harbored high levels of SIV. But there were several startling findings.
The immunoPET method illuminated surprisingly high levels of the SIV antibody in the nasal cavity, the investigators report online today in Nature Methods. "The entire upper respiratory tract is rich with lymphatic tissue, and we just never thought of that," says Timothy Schacker of the University of Minnesota, Twin Cities, who studies how HIV causes disease. "That's a really cool finding."
Villinger was particularly struck by the high levels of SIV in the genital tract of males, given that sexual transmission of the AIDS virus does not occur all that readily. "The epididymis [the tubes that carry sperm] of the monkeys are just lighting up," Villinger says. "It's mind-boggling." The virus also had an unexpected penchant for the lung, an organ that has received relatively little attention from HIV researchers.
Detecting and monitoring the so-called "viral dynamics" of AIDS infection has long required blood sampling or tissue biopsy. In other words, if you wanted to see whether an infection was raging in, say, the mucosa of a monkey's intestines (a known hotspot for SIV replication), it meant having to sample the tissue directly, which in turn meant cutting the monkey open. immunoPET turns viral monitoring into a noninvasive procedure. If it can be adapted to tracking HIV in humans (and researchers are confident that it can), Villinger and his colleagues say it will have broad applications, in everything from the study of the way immunodeficiency viruses develop in the body, to drug and vaccine development.
A quick example: Because the method can be repeated within the same individual, it's easy to imagine how immunoPET might be used to monitor a patient's response to antiretroviral therapy (ART), or other, novel therapeutic approaches. Villinger and his colleagues did exactly this with the monkeys in their study. The figure above figure shows scan results from a chronically infected monkey, before and at 5 weeks of ART. In the head, groin, torso, and bowels, ART was shown to decrease measured viral activity within each region of interest (viral activity is denoted here by what's called standardized uptake value, or "SUV." Higher SUV values correspond to warmer colors in the images. Arrows point to regions where specific PET signals declined during ART.)
"With the current efforts toward HIV eradication or functional cure," write the researchers, "we believe that this method can be useful for determining organ-specific efficacy, which is crucial to the elimination of virally infected cells."