HTLV-1 p12 modulates the levels of prion protein (PrP C ) 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 ^C ) in immune cells.
Methods: Here, we investigated whether HTLV-1 infection affected PrP ^C content in cell lines and primary CD4 ⁺ cells in vitro using flow cytometry and western blot assays.
Results: We found that HTLV-1 infection decreased the expression levels of PrP ^C and HTLV-1 Orf I 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 ^C , which was reflected by IFN type II but not IL-17 expression.
Discussion: These results suggested that PrP ^C 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.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright At least a portion of this work is authored by Isabela Silva De Castro, Cynthia A. Pise-Masison and Genoveffa Franchini on behalf of the U.S. Government and as regards Dr. Silva De Castro, Dr. Pise-Masison and Dr. Franchini and the U.S. Government, is not subject to copyright protection in the United States. Foreign and other copyrights may apply.)