Researchers have found that latent but replication-competent HIV can lie dormant in immune cells in the brain for years. The corresponding study was published in JCI.
The HIV virus targets CD4+ lymphocytes in the body, a type of white blood cell that activates killer T cells, macrophages, and B cells to trigger an immune response. Over time, HIV depletes numbers of CD4+ cells, leading to immunodeficiency.
Previous research shows that latent HIV can hide within some of the remaining CD4+ cells. Researchers, however, have suspected that latent forms of the virus can also hide within the central nervous system in people receiving antiretroviral therapy (ART). However, due to difficulties in accessing and analyzing brain tissues, whether or not latent HIV can hide in the brain has remained unknown.
For the current study, researchers isolated brain cells from macaques infected with simian immunodeficiency virus (SIV)- a close relative of HIV that infects non-human primates. They also isolated brain cells from people with HIV who were on ART and facing a terminal illness. Ultimately, they found that SIV and HIV DNA were detectable in the brain cells of the macaques and human samples.
The researchers concluded that their findings indicate that immune cells in the brain known as microglia can harbor replication-competent HIV. They now hope to conduct further research with the aim of one day targeting and eradicating this reservoir.
The NF-κB signaling pathway controls HIV expression in the body; when it switches off, HIV enters latency in peripheral blood. Unlike HIV in the peripheral blood, however, HIV in the brain is unaffected by the activation of NF-κB signaling. The researchers hope to elucidate why this is the case in further studies. They also hope to understand how large the HIV reservoir is in the brain to best be able to target it and eradicate the condition.
“HIV is very smart,” said senior author Guochun Jiang, Ph.D., assistant professor in the UNC Department of Biochemistry and Biophysics and member of the UNC HIV Cure Center. “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”.”
Sources: EurekAlert, JCI