HIV Persistence in Macrophages
A new approach may be needed to design an effective cure for HIV because of the virus’ ability to survive anti-retroviral therapy (ART), according to new research. The paper, published in Nature Medicine and completed by researchers at the University of North Carolina’s (UNC) Division of Infectious Diseases, demonstrates that the virus can persist in macrophages through treatment and can propagate once treatment is complete.
Most current therapies for HIV involve attempting to remove the virus from T-cells, a vital component of the human immune system. However, this study reveals why this treatment approach can often fail by demonstrating that macrophages, white blood cells found in the brain, bone marrow, liver, and other tissues, can foster the virus throughout therapy.
“These results are paradigm changing because they demonstrate that cells other than T-cells can serve as a reservoir for HIV,” said Jenna Honeycutt, Ph.D., lead author and researcher at the UNC Division of Infectious Diseases. “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 work builds on previous research from UNC’s School of Medicine, which used mouse models to show how macrophages could sustain the virus even in the absence of T-cells. To further this research, Honeycutt and her team investigated how HIV replication was suppressed in macrophages during treatment and how the virus could rebound once the therapy was stopped.
“This is the first report demonstrating that tissue macrophages can be infected and that they respond to antiretroviral therapy,” Honeycutt said. “In addition, we show that productively infected macrophages can persist despite ART 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.”
The team wish to continue their work in future to uncover how macrophages support HIV persistence and how they are able to evade current therapies. By understanding the mechanism by which HIV survives treatment, the team are hopeful that a new approach to treating HIV might be developed and, ultimately, a cure.