Researchers identify a new HIV reservoir

April 17, 2017
HIV infecting a human cell. Credit: NIH

HIV cure research to date has focused on clearing the virus from T cells, a type of white blood cell that is an essential part of the immune system. Yet investigators in the Division of Infectious Diseases at the University of North Carolina School of Medicine have found the virus persists in HIV-infected macrophages. Macrophages are large white blood cells found in tissues throughout the body including the liver, lung, bone marrow and brain. The discovery of this additional viral reservoir has significant implications for HIV cure research. These findings were published in Nature Medicine on Monday, April 17.

"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 postdoctoral research associate in 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."

Last spring, this laboratory lead by J. Victor Garcia, Ph. D., professor of medicine, microbiology and immunology at UNC School of Medicine, demonstrated the ability of to support HIV replication in vivo in the total absence of human T cells. But how macrophages would respond to antiretroviral therapy (ART) and whether macrophages represented a reservoir for HIV after treatment were unknown.

Macrophages are myeloid lineage cells that have been implicated in HIV pathogenesis and in the trafficking of virus into the brain. Using a humanized myeloid-only mouse (MoM) model devoid of T cells, Garcia and his team showed that ART strongly suppresses HIV replication in tissue macrophages. Yet when HIV treatment was interrupted, viral rebound was observed in one third of the animals. This is consistent with the establishment of persistent infection in tissue macrophages.

"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."

Now that Garcia and his team know HIV persists in macrophages, the next step will be to determine what regulates HIV persistence in tissue macrophages, where in the body persistently infected macrophages reside during HIV treatment and how macrophages respond to possible therapeutic interventions aimed at eradicating HIV from the body.

Explore further: Researchers prove HIV targets tissue macrophages

More information: HIV persistence in tissue macrophages of humanized myeloid-only mice during antiretroviral therapy, Nature Medicine (2017). nature.com/articles/doi:10.1038/nm.4319

Related Stories

Researchers prove HIV targets tissue macrophages

March 8, 2016

Investigators in the Division of Infectious Diseases at the University of North Carolina School of Medicine have clearly demonstrated that HIV infects and reproduces in macrophages, large white blood cells found in the liver, ...

Insulin resistance reversed by removal of protein

November 3, 2016

By removing the protein galectin-3 (Gal3), a team of investigators led by University of California School of Medicine researchers were able to reverse diabetic insulin resistance and glucose intolerance in mouse models of ...

The immune system-body weight connection

August 24, 2016

A primary role of the immune system is fighting off harmful bacteria and viruses. However, recent studies have revealed additional roles of immune cells in other important host functions, such as controlling body weight.

Recommended for you

Study reveals how HIV virus destroys lung tissue

May 17, 2017

Up to 30 percent of HIV patients who are appropriately treated with antiretroviral therapies develop the chronic lung disease emphysema. New research from Weill Cornell Medicine investigators has uncovered a mechanism that ...

Researchers take an important step toward an HIV vaccine

May 17, 2017

Researchers from the University of Copenhagen have developed a strategy that can revolutionize vaccine design. The new strategy is used to develop vaccines that can prevent HIV infection and the development of AIDS.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.