HIV-1, the virus responsible for AIDS, has long been recognized for its devastating effects on the immune system. Recent studies have uncovered its complicity with neurocognitive disorders, demonstrating how it infiltrates the central nervous system. A new research study has established the role of amyloid fibrils, particularly α-synuclein and Aβ peptides, as enhancers of HIV-1 infection, linking viral entry to established markers of neurodegenerative diseases.
Amyloid fibrils are best known for their association with neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases. This study highlights their unexpected role as facilitators of HIV-1 entry and replication across human T cells, macrophages, and microglia, which are cells of the immune system residing within the brain.
The research involved detailed analyses wherein samples containing amyloid fibrils reinforced the ability of HIV-1 to infect key cell types. "α-synuclein and Aβ fibrils interact with HIV-1 particles and promote virion attachment and fusion with target cells," the authors note, emphasizing the complex interplay between these fibrils and the virus.
Despite the traditionally understood negative surface charge of these fibrils, which might inhibit such interactions, the structure of the amyloids appears to favor binding and subsequent entry of the virus. This mechanism sheds light on previously poorly understood pathways of HIV-1 invasion of the brain—particularly important considering the alarming rate of HIV-associated neurocognitive disorders (HAND) affecting 30 to 60% of people living with HIV.
Using sophisticated infectious assays, the researchers could quantify how much these fibrils actually facilitated the viral infection rates. They found significant increases, with α-synuclein fibrils exhibiting the most pronounced effect. “The enhancing effects of human brain extracts on HIV-1 infection correlated with their binding to Thioflavin T, a dye commonly used to stain amyloids,” the researchers clarified, indicating the biological relevance of the findings.
The investigation also uncovered the role of human brain lysates, demonstrating their ability to increase HIV-1 infection, hinting at the clinical significance of these interactions. Previous research has linked HIV-1 to amyloid accumulation, meaning the presence of one could catapult the presence of the other, leading to increased complications for affected individuals.
These insights could reshape therapeutic strategies for combating the cognitive decline tied to HIV-1. “These results suggest a detrimental interplay between HIV-1 and brain amyloids, which may contribute to the development of neurodegenerative diseases,” the authors highlight, urging for more research.
Overall, this study bridges our knowledge of neurodegenerative diseases and virology, indicating future research could potentially develop targeted treatments focusing on these amyloid interactions. With the urgency imposed by the rising prevalence of HAND, innovative strategies are needed to mitigate this growing public health concern.