Even when HIV is well-controlled with medication, a notable number of people living with the virus experience cognitive difficulties. Now, researchers have pinpointed genetic signatures in reprogrammed skin cells that may explain why, offering a fresh avenue for understanding-and possibly treating-these lasting effects.
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Approximately 25-50% of people with HIV worldwide experience neurocognitive disorders, despite effective treatment.
A study published in JCI Insight details how scientists at Weill Cornell Medicine transformed skin cells from individuals with and without HIV into functioning neurons. By comparing these lab-grown cells, they discovered key differences in gene activity patterns between the two groups.
“These findings give us a foundation for future studies of how certain genes and biological pathways may contribute to this form of cognitive impairment,” said dr. Teresa H.Evering, an assistant professor of medicine in the Division of Infectious Diseases at Weill Cornell Medicine and an infectious disease physician at NewYork-Presbyterian/Weill Cornell Medical Center.
How HIV Impacts Cells Beyond Direct Infection
The research highlights that the cognitive issues aren’t necessarily caused by the virus directly infecting brain cells. Rather, the study suggests there are systemic effects on cells, even when the virus is suppressed, and these effects aren’t simply due to direct infection of brain cells.
Key Genetic Clues Emerge
Among the genes showing altered activity, the inflammatory gene IFI27 was found to be more active in neurons derived from people with HIV. Conversely,three other genes – FOXL2NB,FOXL2,and LINC01391 – exhibited reduced expression levels,all of which have been linked to cognitive impairment. Researchers are now planning further investigations into the specific roles of these genes in HIV-related cognitive changes, utilizing more complex model systems.
Did you know? The reprogramming technique used in this study allows researchers to create neurons that retain characteristics of the donor’s age, providing a more accurate model for studying age-related cognitive decline.
Philipp N. Ostermann et al, Transcriptional signature of induced neurons differentiates virologically suppressed people with HIV from people without HIV, JCI insight (2025). DOI: 10.1172/jci.insight.190445
Journal information: JCI Insight
