It's like using heat cameras to catch criminals on the run, but it finds HIV instead. A novel scanning technique is enabling researchers to pinpoint where in the body HIV is lurking.
"This could really help with the research for a functional cure," says Alan Winston of Imperial College London, who was not involved in the study.
Today's potent drug treatments can eradicate HIV from the blood, but the virus must survive elsewhere in the body, because it returns when people stop taking these drugs.
It has been assumed that the virus hides out in immune cells at various "sanctuary sites", either replicating very slowly or becoming completely dormant. Supporting this, biopsies reveal the virus in sites such as patches of immune tissue in the gut.
Sanctuary sites
One strategy to eradicate HIV completely might be to somehow wake up the hiding virus and then kill it. Research into this "kick and kill" strategy is ongoing, but little is known about which sanctuary sites are the most important, what the virus is doing there and whether existing drugs can reach the sites.
Francois Villinger of Emory University in Atlanta and colleagues wondered if a PET scanning approach, which is also used to show the spread of cancer, could reveal the location of the virus. This idea was prompted by the discovery of an antibody that binds strongly to SIV, the monkey version of HIV.
To test the idea, the team injected radioactive antibodies into three monkeys with SIV that were being treated with antiviral drugs. PET scanning, which can detect the location of radiation sources within the body, revealed the viral protein, called gp120, in a range of sites including the nose, lungs, gut, genitals and lymph nodes in the armpits and groin. The antibody could not get into the brain, however, which is thought to be another sanctuary site.
The scans were not detailed enough to reveal which specific cells the virus protein was in, but tests after the monkeys were killed confirmed that the virus was present in the immune cells of the areas identified by the scan.
Kick and kill
Although the technique won't show up a virus that is completely dormant, just being able to see where there is low viral replication is a major advance, says Winston. "It's the first paper that has allowed us to visualise viral reservoirs."
The next step would be to develop antibodies that can recognise the gp120 protein made by the human strain of the virus. Scans made using these could aid researchers working on kick-and-kill strategies, and help investigate the rare cases where people seem to have been cured of HIV.
This has been claimed for a handful of people who were given bone marrow transplants from donors whose immune cells are resistant to HIV, as well as for an infant who was given antiviral drugs straight after birth.
Initially after that child – the so-called Mississippi baby – was taken off the drugs, there was no virus detectable in her blood, and her doctor claimed a cure. Unfortunately, after four years the virus returned and she had to restart drug treatment.
The PET scanning technique could help in such cases, Villinger speculates, by revealing if the virus is present in sanctuary sites.
Journal reference: Nature Methods, DOI: 10.1038/NMETH.3320
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