HIV Found to Persist in Infected Macrophages

The discovery means the virus is capable of persisting beyond the body's T cells — and future treatment must address that.

Though human immunodeficiency virus (HIV) has become significantly more manageable with the progression of daily treatment such as antiretroviral therapy (ART), an actual cure for the disease still does not exist.

But researchers from the University of North Carolina (UNC) School of Medicine’s Division of Infectious Diseases have made a pathological discovery that may aid the search for an HIV cure. While research has previously focused on clearing the virus’ infection of the body’s T cells, the UNC researchers have found HIV persists in infected macrophages — while blood cells found in major organs’ tissues.

The revelation and what it means for curing HIV is clear: the virus’ location is larger than previously thought.

“These results are paradigm changing because they demonstrate that cells other than T cells can serve as a reservoir for HIV,” Jenna Honeycutt (pictured), PhD, lead author and postdoctoral research associate in the UNC Division of Infectious Diseases, said. “The fact that HIV-infected macrophages can persist means that any possible therapeutic intervention to eradicate HIV might have to target two very different types of cells.”

The researchers’ discovery of macrophage serving as a reservoir was preceded by their own work last spring, when they were able to demonstrate tissue macrophages’ ability to support HIV replication in vivo in the total absence of human T cells.

The previous study, led by J. Victor Garcia, PhD, professor of medicine, microbiology and immunology at the UNC School of Medicine, did not indicate how macrophages would respond to ART. To study the interaction, Garcia and his team used humanized myeloid-only mouse (MoM) models devoid of T cells.

ART was capable of strongly suppressing HIV replication in the tissue macrophages, but viral rebound was observed in one-third of the models when the HIV treatment was interrupted.

This discovery was consistent with concept of persistent infection in tissue macrophages, and perhaps more importantly, was the first documented report of tissue macrophage HIV infection and response to ART, Honeycutt said.

“In addition, we show that productively infected macrophages can persist despite ART,” Honeycutt said. “And most importantly, that they can reinitiate and sustain infection upon therapy interruption even in the absence of T cells — the major target of HIV infection.”

Next for the team is looking into what regulates the virus’ persistence in tissue macrophage, where infected macrophages reside during treatment, and how macrophages respond to the current therapeutic interventions intended to eventually eradicate HIV from patients’ bodies.

A press release regarding the study was made available.

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