Authors: Martha Powell, Future Science Group
Researchers from the University of North Carolina School of Medicine (NC, USA) have discovered that HIV can persist in infected macrophages; a change from previous research focusing primarily on T cells. The discovery of this additional viral reservoir may have significant implications for HIV research moving forwards.
Last year the team reported findings demonstrating the ability of tissue macrophages to support HIV replication in the absence of T cells in vivo. Building on this, their latest study, published in Nature Medicine, investigated the response of macrophages to antiretroviral therapy (ART) and determined whether macrophages were a reservoir for HIV.
The team utilized a humanized myeloid-only mouse model, which is devoid of T cells, to demonstrate that HIV replication in tissue macrophages was suppressed by ART. This was determined by a measuring plasma viral load and the levels of cell-associated viral RNA and DNA, both of which decreased with ART.
However, when ART treatment was stopped the researchers discovered that viral rebound occurred in a third of animals, and this correlated with the establishment of persistent infection in macrophages.
Lead author Jenna Honeycutt (University of North Carolina) commented: “These results are paradigm changing because they demonstrate that cells other than T cells can serve as a reservoir for HIV. 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.”
This study represents the first direct evidence of HIV persistence in tissue macrophages in vivo. The team hopes to carry out further research to determine the factors regulating HIV persistence in tissue macrophages, where persistently-infected macrophages reside during ART and to investigate possible therapeutics targeting macrophages.
Honeycutt concluded: “This is the first report demonstrating that tissue macrophages can be infected and that they respond to ART. 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.”
Sources: Honeycutt JB, Thayer WO, Baker CE et al. HIV persistence in tissue macrophages of humanized myeloid-only mice during antiretroviral therapy. Nat. Med. doi:10.1038/nm.4319 (2017) (Epub ahead of print); http://news.unchealthcare.org/news/2017/april/unc-researchers-identify-a-new-hiv-reservoir