New White Blood Cell Subtype as HIV Reservoir Identified

Scientists from Johns Hopkins University have identified myeloid cells, a subset of white blood cells including monocytes and macrophages, can act as HIV reservoirs in patients who have been virally suppressed for years on antiretroviral therapy (ART) and can be reactivated and infect new cells. 

Their novel findings, published in the journal Nature Microbiology, strongly suggest that myeloid cells could be another potential target in developing strategies to eradicate HIV.

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The Limitations of Antiretroviral Therapy

Antiretroviral therapy is the standard treatment for HIV patients which combines two or more antivirals to increase potency and reduce the likelihood of the virus developing resistance. Despite ART showing its efficacy to control HIV progression, the virus may still exist in cells that are in a resting, or latent, state, creating an HIV reservoir. 

Among them, CD4 T cells are the most well-studied HIV reservoir. However, targeting CD4 T cells alone could not eradicate HIV, thus, Identifying more HIV reservoirs is critical to curing efforts, before latent HIV reactivation if people stop taking antiretroviral medications.

Monocytes are immune cells that circulate in the blood for about 3 days before traveling to tissue in various parts of the body, including the brain, where they can mature into macrophages. So far, there is no other evidence showing latent HIV in the short-lived monocytes and longer-lived monocyte-derived macrophages can become active again and infect other cells.  

Promising Target to Develop Antiviral Strategy

In the current study, the investigators measured HIV DNA in myeloid cells in a sample of 30 participants with HIV that were virally suppressed and had been on ART for at least 5 years. HIV genetic material in monocytes and macrophages was detected, though at a much lower level than those observed in CD4 T cells. 

They then isolated monocytes from blood samples taken from 10 participants and nurtured the monocytes in cultures that contained antiretroviral drugs, to replicate the participants’ baseline physical state. After the monocytes differentiated into macrophages, the researchers introduced an immune-activating agent and then added fresh white blood cells to allow for the virus to spread to new cells.  

At the end of the study, cultures collected from half of the participants had detectable HIV genetic material in monocyte-derived macrophages that could be reactivated to infect other cells and produce more virus, suggesting the myeloid cells are the reservoir for the virus to persist for years.

Overall, it may be said the myeloid cells would become the next focus of scientists to modify current ART, however, the investigators also pointed out their limitations in sample size and population diversity.

Author

Nai Ye Yeat