Like a predator lurking in the shadows, waiting for its prey to take down their guard before striking, HIV lurks in the body in hidden places, evading drugs and escaping detection by the immune system. As soon as the patient stops taking their medication, the virus springs back into action and rapidly spreads throughout the body, fatally attacking vulnerable cells along the way.
It is because of these hiding skills that researchers believe a cure currently eludes us, but despite significant advances in our understanding of this feature of infection, teasing out the virus’ favorite hideouts has been challenging. Now, scientists have made a huge leap forward in this field by producing the first whole-body map of active viral replication in a living animal. Not only did this reveal that the primate version of HIV, SIV, lingered in some surprising spots in infected monkeys, but also that antiviral drugs alter its distribution.
Importantly, this technique should be applicable to humans, leading researchers to believe it could be a valuable tool in the search for a cure or a long-awaited vaccine. That’s because researchers think it should be possible to coax HIV out from hiding and then attack it with drugs, eradicating the lingering supply from the body. Researchers have been investigating this idea for some time now and although promising compounds have been identified that could awaken dormant HIV, it has not been clear which hideouts are most important to target and whether drugs could even reach these.
In the hope of shedding light on this, a team of researchers led by Emory University’s Francois Villinger began to investigate the possibility of using a specialized imaging technique, known as positron emission tomography (PET), to reveal SIV’s location throughout the body. This procedure relies on the use of radioactive substances to act as tracers, which are then picked up by a special type of camera. The researchers therefore attached a radioactive tag to an antibody specific for a part of the virus and then administered it to SIV-infected monkeys.
Alongside backing up what biopsy and blood samples previously revealed about HIV’s whereabouts, such as a high presence in the gut and lymph nodes, the scans also produced some unexpected findings. For example, actively replicating virus was found in the nose and lungs, areas that had been previously overlooked by scientists. Furthermore, when the researchers treated the animals with antiviral drugs, it was evident that some tissues still harbored active virus, despite it dropping down to undetectable levels in the blood.
If this technique can be adapted for humans using HIV-specific antibodies, then it could turn out to be an invaluable tool. For example, it could help identify areas of the body in which HIV maintains quiet reservoirs of infected cells despite the action of drugs, which could allow researchers to tailor treatments to specifically target these areas. Alternatively, imaging could reveal which drugs are most effective at waking up dormant HIV and researchers could focus on developing these treatments further.
[Via Nature Methods, Science and New Scientist]
3