HIV News - HIV Genomes in Monocytes Apr 12, 2023 1 year, 1 week, 6 days, 22 hours, 27 minutes ago
HIV News: In the pursuit of HIV eradication, scientists have been examining various hiding places or reservoirs where the virus can store its genetic material. Recent research conducted by a team from Johns Hopkins Medicine has discovered evidence that HIV genomes can persist in a stable reservoir within circulating white blood cells called monocytes. This discovery may provide a new direction for improving therapies and eventually curing HIV, which affects over 34 million people worldwide.
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Studies and
HIV News coverages show that current antiretroviral drugs can successfully suppress HIV to nearly undetectable levels, but they have not led to the total eradication of the virus. The study found evidence that blood samples from individuals with HIV undergoing long-term standard antiretroviral therapy contained monocytes harboring stable HIV DNA capable of infecting neighboring cells.
Monocytes are circulating immune cells with a short lifespan that eventually develop into macrophages, immune cells capable of engulfing and destroying foreign elements such as viruses and bacteria. Scientists have long known that HIV stashes its genome most often in a type of immune cell called a CD4+ T-cell, which are known as reservoirs.
The goal of HIV eradication is to find biomarkers for cells that harbor the HIV genome and eliminate those cells. To further study the role of monocytes and macrophages as HIV reservoirs, the study team obtained blood samples from 10 men with HIV, all of whom were taking long-term standard antiretroviral medications. They extracted blood cells from the samples and grew them in the laboratory, where the monocytes transformed into macrophages. All 10 men had detectable HIV DNA in their monocytes-turned-macrophages, but at levels 10 times lower than those found in their CD4+ T cells, the well-established HIV reservoir.
To determine if HIV genomes were present in monocytes before they transformed into macrophages, the team used an experimental assay to detect intact HIV genomes in monocytes.
The study team found HIV DNA in the CD4+ T cells and monocytes of all 30 participants. They also isolated HIV produced by infected monocytes from half of the participants, which was capable of infecting CD4+ T cells.
The study team utilized two independent techniques, quantitative viral outgrowth assay (QVOA) and intact proviral DNA assay (IPDA), to quantify the monocyte reservoir in people with HIV.
Three of the participants had their blood examined several times over the four-year study period, and each time, the scientists found HIV DNA and infectious virus produced by their monocyte-derived macrophages. These study findings suggest that monocytes may be a stable reservoir of HIV.
In further research, the Johns Hopkins team plans to pinpoint the subset of monocytes found to harbor HIV DNA and the source of these infected cells. This study emphasizes the importance of including monocytes and macrophages in HIV cure efforts, as they may contribute to the size of the HIV reservoir and play a role in viral rebound after treatment interruption.
Persistent cellular reservoirs of latent HIV, such as those found in monocytes and macrophages, are a significant obstacle to v
iral eradication.
The study findings demonstrate that around 40–50% of virologically suppressed people with HIV harbor reactivatable latent virus in monocyte-derived macrophages. This is notable as monocytes have often been disregarded in cure-based efforts.
The study found that the monocyte reservoir is stable and persistent in long-term virologically suppressed people with HIV, which supports the hypothesis that bone marrow containing latent virus seeds blood monocytes, or that ongoing replication occurs in an unknown tissue, leading to consistent infection of circulating monocytes.
This research highlights the importance of myeloid cells as an HIV reservoir, and further studies are needed to understand the mechanisms driving their persistence and potential strategies for their elimination.
This study provides direct evidence that monocyte reservoirs should be included in HIV cure efforts.
In conclusion, the discovery of HIV genomes in monocytes as a stable reservoir presents a new target for HIV eradication. This breakthrough may lead to the development of improved therapies and, ultimately, a cure for the millions of people affected by HIV worldwide. Future research will focus on understanding the role of monocytes in the maintenance of tissue macrophage reservoirs and identifying the specific subset of monocytes harboring HIV DNA.
With this newfound knowledge, researchers can now work towards developing strategies to target and eliminate these monocyte reservoirs, bringing us one step closer to the ultimate goal of complete HIV eradication. This study also highlights the importance of considering all potential reservoirs in the ongoing quest for an HIV cure and serves as a reminder that a comprehensive understanding of the virus's behavior and hiding places is crucial for developing effective treatments.
The study findings were published in the peer reviewed journal: Nature Microbiology.
https://www.nature.com/articles/s41564-023-01349-3
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