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Discovery That HIV Can Lie Dormant in Brain Moves Research Closer to Eradication
Scientists isolate cells where HIV Hides

New research suggests that the brain could be a hiding place for latent HIV in the human body. Scientists said that microglial cells (MG), an immune cell in the brain, can harbor the virus. Specialized immune cells, microglial cells can survive about ten years in the brain, and HIV can infect them. Some of the cells become dormant. If antiretroviral therapy (ART), the treatment for HIV, is stopped, the virus can rebound from these cells and reactivate the infection, which can then progress to from HIV infection to AIDS.

In their abstract, the researchers wrote, “Brain microglia (MG) may serve as a human immunodeficiency virus 1 (HIV) reservoir and ignite rebound viremia following cessation of antiretroviral therapy (ART), but they have yet to be proven to harbor replication-competent HIV. Here, we isolated brain myeloid cells (BrMCs) from nonhuman primates and rapid autopsy of people with HIV (PWH) on ART and sought evidence of persistent viral infection. BrMCs predominantly displayed microglial markers, in which up to 99.9% of the BrMCs were TMEM119+ MG. Total and integrated SIV or HIV DNA was detectable in the MG, with low levels of cell-associated viral RNA. Provirus in MG was highly sensitive to epigenetic inhibition. Outgrowth virus from parietal cortex MG in an individual with HIV productively infected both MG and PBMCs. This inducible, replication-competent virus and virus from basal ganglia proviral DNA were closely related but highly divergent from variants in peripheral compartments. Phenotyping studies characterized brain-derived virus as macrophage tropic based on the ability of the virus to infect cells expressing low levels of CD4. The lack of genetic diversity in virus from the brain suggests that this macrophage-tropic lineage quickly colonized brain regions. These data demonstrate that MG harbor replication-competent HIV and serve as a persistent reservoir in the brain.”

Researchers developed techniques to isolate pure brain myeloid cells from the cells in immune response when HIV attacks in brain tissue. By isolating brain microglia (MG) from humans on long-term, antiretroviral therapy (ART), researchers showed the presence of replication-competent HIV, which could progress into AIDS, within the cells. Their data showed that MG harbor replication-competent HIV and serve as a reservoir in the brain. The discovery is a huge step forward in advancing research aimed at eradicating HIV. Read the study here.

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