Cerebrospinal fluid from HAM/TSP patients with rapid evolution affects mitochondrial DNA transcription and structure in human glioblastoma cell lines

Human T-lymphotropic virus 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a progressive neurodegenerative disease impacting motor and sensorial functions. While the cerebrospinal fluid (CSF) alterations have been used to identify biomarkers for this disease, the effects of HTLV-1 CSF on neural cells remain unexplored. Herein, we investigated the impact of CSF from HTLV-1 infected patients on glioblastoma cell lines. CSF samples were obtained from HTLV-1 asymptomatic carriers (HAC) (n=13), and HAM/TSP patients (n=21) categorized according to the speed of disease progression: very slow (HAMvs), typical (HAMt), and rapid (HAMr). RNA sequencing of glioblastoma cells treated with HTLV-1 CSF revealed notable gene expression changes, particularly with HAMr CSF, which caused significant downregulation of mitochondrial DNA transcripts. Confocal microscopy showed phenotypical changes in the mitochondrial network: astrocytes exposed to HAMr CSF exhibited a less complex mitochondrial network compared to CSF from other patient groups. It is characterized by reduced mitochondrial branching, fewer junctions per branch length, and slightly increased branch diameter. Compared to untreated cells, HTLV+ CSF disturbed mitochondrial metabolism. However, these changes are limited at the metabolic level and do not appear to vary significantly with HTLV donor status. In conclusion, our findings suggest that HTLV+ CSF induces mitochondrial reorganization in glioblastoma cells, potentially helping to compensate for the stress caused by the CSF exposure. Bulk RNA-seq profiling of U87-MG cells incubated for 6 hours and 24 hours with cerebrospinal fluid from HAM/TSP patients with different speed of disease progression.