HTLV-1 p12 modulates the levels of prion protein (PrP) in CD4 T cells.

Introduction: Infection with human T cell lymphotropic virus type 1 (HTLV-1) is endemic in Brazil and is linked with pro-inflammatory conditions including HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a chronic neuroinflammatory incapacitating disease that culminates in loss of motor functions. The mechanisms underlying the onset and progression of HAM/TSP are incompletely understood. Previous studies have demonstrated that inflammation and infectious agents can affect the expression of cellular prion protein (PrP) in immune cells.

Methods: Here, we investigated whether HTLV-1 infection affected PrP content in cell lines and primary CD4cells using flow cytometry and western blot assays.

Results: We found that HTLV-1 infection decreased the expression levels of PrP and HTLV-1 encoded p12, an endoplasmic reticulum resident protein also known to affect post-transcriptionally cellular proteins such as MHC-class I and the IL-2 receptor. In addition, we observed a reduced percentage of CD4 T cells from infected individuals expressing PrP, which was reflected by IFN type II but not IL-17 expression.

Discussion: These results suggested that PrP downregulation, linked to both HTLV-1 p12 and IFN-γ expression in CD4 cells, may play a role in the neuropathogenesis of HTLV-1 infection.