HIV can lie dormant in the brain, and discontinuation of treatment can reignite the progression of infection to AIDS, finds a study.
As a part of its life cycle, the human immunodeficiency virus-1 (HIV) inserts a copy of its DNA into human immune cells. Some of these newly-infected immune cells can then transition into a dormant, latent state for a long period of time, which is referred to as HIV latency.
Although current therapies, such as current antiretroviral therapy (ART), can successfully block the virus from replicating further, it cannot eradicate latent HIV. If treatment is ever discontinued, the virus can rebound from latency and lead to AIDS.
Scientists have been searching for where exactly these latent cells are hiding in the body.
The research, published in the Journal of Clinical Investigations, confirms that microglial cells — which are specialised immune cells with a decade-long lifespan in the brain — can serve as a stable viral reservoir for latent HIV.
“We now know that microglial cells serve as a persistent brain reservoir,” said first author Yuyang Tang, Assistant Professor of Medicine in the Division of Infectious Diseases and member of the University of North Carolina HIV Cure Center.
“This had been suspected in the past, but proof in humans was lacking. Our method for isolating viable brain cells provides a new framework for future studies on reservoirs of the central nervous system, and, ultimately, efforts towards the eradication of HIV,” Tang added.
Now that the researchers know that latent HIV can take refuge in microglial cells in the brain, they are now considering plans to target this type of reservoir.
Since latent HIV in the brain is radically different from the virus in the periphery, researchers believe that it has adapted special characteristics to replicate in the brain.
“HIV is very smart,” said senior author Guochun Jiang, Assistant Professor in the UNC Department of Biochemistry and Biophysics.
“Over time, it has evolved to have epigenetic control of its expression, silencing the virus to hide in the brain from immune clearance. We are starting to unravel the unique mechanism that allows latency of HIV in brain microglia”.”
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