A study funded by the NIH underlines the importance of treating the brain in HIV healing strategies
Researchers have found that astrocytes, a type of brain cell, can harbor HIV and then transmit the virus to immune cells that pass from the brain to other organs. HIV migrated from the brain this way, even if the virus was suppressed by combination antiretroviral therapy (cART), a standard treatment for HIV. The study, carried out by researchers from the Rush University Medical Center in Chicago and published in PLOS Pathogens, was funded by the National Institutes of Health.
“This study shows the brain’s crucial role as an HIV reservoir capable of re-infecting the peripheral organs with the virus,” said Dr. Jeymohan Joseph, director of the Department of HIV Neuropathogenesis, Genetics and Therapeutics at the National Institute of Mental Health of the NIH, which co-financed the study. “The results suggest that healing strategies need to consider the role of the central nervous system in eradicating HIV from the body.”
HIV attacks the immune system by infecting CD4 positive (CD4 +) T cells, a type of white blood cell that is vital for the defense against infection. Without treatment, HIV can destroy CD4 + T cells and decrease the body’s ability to trigger an immune response – which eventually leads to AIDS.
cART, which effectively suppresses HIV infections, has helped many people living with HIV to live longer and healthier lives. However, some studies have shown that many patients receiving antiretroviral drugs also show signs of HIV-associated neurocognitive disorders, such as thinking and memory problems. The researchers know that HIV gets into the brain within eight days of infection. However, it is less known whether HIV-infected brain cells can release viruses that can travel from the brain back into the body to infect other tissues.
The brain contains billions of astrocytes that perform a variety of tasks – from supporting communication between brain cells to maintaining the blood-brain barrier. To understand whether HIV can get from the brain to peripheral organs, Lena Al-Harthi, Ph.D.and her research team at Rush University Medical Center transplanted HIV-infected or non-infected human astrocytes into the brain of immunodeficient mice.
The researchers found that the transplanted HIV-infected astrocytes were able to transmit the virus to CD4 + T cells in the brain. These CD4 + T cells then migrated from the brain to the rest of the body and spread the infection to peripheral organs such as the spleen and lymph nodes. They also found that HIV exiting the brain, albeit in lesser amounts, occurred when the animals were given cART. If the cART treatment was interrupted, HIV-DNA / RNA became detectable in the spleen, which indicates a rebound of the virus infection.
“Our study shows that HIV is not included in the brain in the brain – it can and will return to peripheral organs through leukocyte trafficking,” said Dr. Al-Harthi. “It also sheds light on the role of astrocytes in supporting HIV replication in the brain – even with CART therapy.”
This information has a significant impact on HIV healing strategies because such strategies must be able to effectively target and eliminate reservoirs for HIV replication and infection, added Dr. Al-Harthi added.
“HIV remains a major global public health problem and affects 30 to 40 million people around the world. To help patients, we need to fully understand how HIV affects the brain and other tissue-based reservoirs, ”said May Wong, Ph.D., Program Director for NeuroAIDS and Infectious Diseases in the Neuro Environment at the National Institute for Neurological Disorders and Stroke of the NIH, which co-financed the study. “Although additional studies are required that repeat these results, this study brings us one step closer to this understanding.”
Image shows HIV infection of CD4 + T cells in the mouse brain. Human T cells (magenta), human astrocytes (red), HIV (green), nuclei (blue). Arrows indicate the uptake of HIV from astrocytes in T cells. Photo credit: Al-Harthi et al. (2020)
V. Lutgen, S.D. Narasipura, H.J. Barbian, M. Richards, J. Wallace, R. Razmpour, … & L. Al-Harthi (2020). HIV infects astrocytes in vivo and exits the brain to the periphery. PLOS pathogens
About the National Institute of Mental Health (NIMH): The mission of the NIMH is to change the understanding and treatment of mental illnesses through basic research and clinical research and to pave the way for prevention, recovery and healing. More information can be found on the NIMH website.
The National Institute for Neurological Disorders and Stroke (NINDS) is the nation’s leading donor for brain and nervous system research. The mission of NINDS is to gain basic knowledge of the brain and nervous system and to use this knowledge to reduce the burden of neurological diseases.
About the National Institutes of Health (NIH): NIH, the National Medical Research Agency, includes 27 institutes and centers and is part of the United States Department of Health and Human Services. The NIH is the most important federal agency that conducts and supports basic medical research, clinical research and translational research and investigates the causes, treatments and remedies for common and rare diseases. For more information about NIH and its programs, visit the NIH website.
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