Research conducted by scientists at Weill Cornell Medicine has shed new light on the genetic factors that may contribute to cognitive impairment in individuals living with HIV. The study utilized skin cells reprogrammed into neurons to identify genetic signatures linked to HIV infection, even among those who have effectively suppressed the virus through treatment. The findings were published in the journal JCI Insight.
The research team collected fibroblast cells, a type of connective tissue cell, from the skin of six individuals who are virologically suppressed due to HIV treatment, as well as from seven age- and sex-matched individuals without the virus. By applying advanced cell-reprogramming techniques, the researchers transformed these fibroblasts into neurons. They discovered significant differences in gene activity between neurons derived from the HIV-positive participants and those from the control group. Some of these differences echoed findings from previous studies involving post-mortem brain samples, while others were new, potentially revealing fresh insights into the causes of HIV-related cognitive deficits.
Understanding the Impact of HIV on the Brain
Dr. Teresa H. Evering, an assistant professor of medicine in the Division of Infectious Diseases at Weill Cornell Medicine, emphasized the importance of these findings. “These findings give us a foundation for future studies of how certain genes and biological pathways may contribute to this form of cognitive impairment,” she stated.
HIV can infiltrate a person’s central nervous system and infect various brain cells, including immune cells known as microglia and supportive astrocytes. Even with effective antiretroviral therapy that suppresses the virus to undetectable levels in the blood, HIV can persist in the brain. This chronic infection and the resulting inflammation can lead to various cognitive issues, including memory problems, difficulty concentrating, mood disturbances, and slowed movements. Research indicates that neurocognitive disorders affect between 25% and 50% of people living with HIV worldwide, with prevalence rates varying based on different populations and study settings.
Challenges and Innovative Approaches in Research
Despite advancements in HIV treatment, no effective therapies currently address the neurocognitive effects of the infection. This gap can be attributed to the complexities involved in studying the mechanisms by which HIV affects neurons, particularly in traditional mouse models and post-mortem analyses.
Dr. Evering’s research offers a novel approach to understanding these mechanisms. The team successfully induced the sampled fibroblasts to express genes that allowed them to develop into neurons while retaining age-related characteristics from the original donors. The notable differences in gene activity between the induced neurons from those with HIV and those without suggest that even in virologically suppressed individuals, HIV has profound systemic effects on cells. Importantly, because these neurons originated from skin cells, the gene expression variations likely reflect broader implications of HIV infection rather than direct exposure to infected brain cells.
Among the genes showing altered expression, the inflammatory gene IFI27 was found to be more active in individuals with HIV. Conversely, three other genes—FOXL2NB, FOXL2, and LINC01391—exhibited reduced expression levels associated with cognitive impairment. The researchers aim to conduct further studies to explore the effects of these genes in more depth and investigate complex model systems to enhance understanding of HIV’s impact on cognitive health.
This groundbreaking research not only highlights the intricate relationship between HIV and cognitive functioning but also paves the way for future studies aimed at developing targeted interventions for those affected by HIV-related cognitive impairments.
