HIV-1 brain infection causes cerebral white matter damage and the underlying mechanisms are not fully understood. Toxic virus trans-activator of transcription (Tat) protein can be released to the extracellular space during disease. Tat increases Kv1.3 current in rat oligodendrocytes via downregulation of channel protein phosphorylation. Tat-induced oligodendrocyte and myelin injury can be blocked by specific Kv1.3 antagonists or by knockdown of Kv1.3 gene.