T cells alone are sufficient to establish and maintain HIV infection in the brain

June 4, 2018, University of North Carolina Health Care
Scanning electron micrograph of a human T lymphocyte (also called a T cell) from the immune system of a healthy donor. Credit: NIAID

A new study by University of North Carolina School of Medicine researchers has found that T cells, a type of white blood cell and an essential part of the immune system, are sufficient by themselves to establish and maintain an HIV infection in the brain.

"These results are paradigm changing," said co-corresponding author J. Victor Garcia, Ph.D., Oliver Smithies Investigator, professor of Medicine and a member of the UNC Institute for Global Health and Infectious Diseases, the UNC Center for AIDS Research and the UNC Lineberger Comprehensive Cancer Center. "We have demonstrated for the first time that infection of the can be established and maintained by both human macrophages and T ."

The study, published today in the Journal of Clinical Investigation, builds upon previous work by the same group of researchers, which found that the virus persists in HIV-infected macrophages and demonstrated the ability of tissue macrophages to support HIV replication in vivo in the total absence of human T cells. Macrophages are large found in tissues throughout the body including the liver, lung, bone marrow and brain.

HIV/AIDs researchers long believed that are critical for HIV infection of the central nervous system. But more recent research indicates that HIV infection in cerebral spinal fluid can originate from both T cells and/or macrophages.

To directly address whether or not T cells contribute to the seeding and persistence of HIV infection in the brain, researchers in the laboratories of Angela Wahl, Ph.D. and Garcia used a humanized T-cell only mouse model to determine whether or not myeloid cells are essential for HIV infection of the brain.

The study's lead author is Jenna B. Honeycutt, Ph.D., a postdoctoral research associate in the division of infectious diseases at UNC and the UNC Center for AIDS Research.

"In our studies we show that T cells are a major target of HIV infection in the brain, both in the presence and in the absence of ," said Honeycutt. "In addition we describe a previously unknown phenomenon that occurs in the central nervous system rapidly after infection—specifically, a significant depletion of CD4 T cells within 1-2 weeks of infection in the brain.

"This has previously been reported for mucosal tissues, but has not been reported previously in the brain. We also report that the depletion of CD4+ T cells in the brain can be efficiently reversed by antiretroviral therapy," said Honeycutt, whose work on this research recently led to her being awarded the Lineberger Comprehensive Cancer Center's Pagano Award.

Another significant aspect of this work is that it establishes that the brain is not an immune-privileged site as previously thought, and that the possibility of a persistent reservoir for HIV in the brain has been severely underestimated.

"Despite effective suppression of HIV virus in the blood by antiretroviral therapy, we were still able to detect virus in the brain in more than 65 percent of the brains analyzed," said Wahl, who is co-corresponding author of the study. "These results indicate that the brain may be an important reservoir for HIV in patients that should be targeted by HIV cure approaches. Future studies will be needed to determine if the virus that persists in the brain during ART is able to re-ignite the if ART is removed."

Explore further: Researchers identify a new HIV reservoir

Related Stories

Researchers identify a new HIV reservoir

April 17, 2017
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 ...

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, ...

HIV exports viral protein in cellular packages

February 15, 2018
HIV may be able to affect cells it can't directly infect by packaging a key protein within the host's cellular mail and sending it out into the body, according to a new study out of a University of North Carolina Lineberger ...

Study shows how HIV breaches macrophage defenses, could be step towards cure

January 25, 2017
A team led by UCL researchers has identified how HIV is able to infect macrophages, a type of white blood cell integral to the immune system, despite the presence of a protective protein. They discovered a treatment that ...

HIV lies dormant in brain, increasing risk of dementia, but how?

May 23, 2018
The HIV virus, which causes AIDS, has long been known to target and disable cells of the immune system, which are responsible for fighting off invading microorganisms and for suppressing malignant cancers. More recently, ...

Immune cells proposed as HIV hideout don't last in primate model

October 31, 2014
Where does HIV hide? Antiretroviral drugs can usually control the virus, but can't completely eliminate it. So any strategy to eradicate HIV from the body has to take into account not only the main group of immune cells the ...

Recommended for you

New study shows how gut immune cells are kept in control

June 22, 2018
Every day, the human gut works on a fine-tuned balance that ensures the retention of essential nutrients while preventing infection by potential armful microbes. Contributing to this surveillance system is a specialised group ...

Human immune 'trigger' map paves way for better treatments

June 21, 2018
A discovery about how human cells are 'triggered' to undergo an inflammatory type of cell death could have implications for treating cancer, stroke and tissue injury, and immune disorders.

Our intestinal microbiome influences metabolism—through the immune system

June 21, 2018
Research tells us that the commensal or "good" bacteria that inhabit our intestines help to regulate our metabolism. A new study in fruit flies, published June 21 in Cell Metabolism, shows one surprising way they do this.

Fetal T cells are first responders to infection in adults

June 20, 2018
Cornell University researchers have discovered there is a division of labor among immune cells that fight invading pathogens in the body.

How a thieving transcription factor dominates the genome

June 20, 2018
One powerful DNA-binding protein, the transcription factor PU.1, steals away other transcription factors and recruits them for its own purposes, effectively dominating gene regulation in developing immune cells, according ...

Severe stress may send immune system into overdrive

June 19, 2018
(HealthDay)—Trauma or intense stress may up your odds of developing an autoimmune disease, a new study suggests.

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.