AUTHOR=Silva De Castro Isabela , Granato Alessandra , Mariante Rafael Meyer , Lima Marco Antonio , Leite Ana Claudia Celestino , Espindola Otávio de Melo , Pise-Masison Cynthia A. , Franchini Genoveffa , Linden Rafael , Echevarria-Lima Juliana TITLE=HTLV-1 p12 modulates the levels of prion protein (PrPC) in CD4+ T cells JOURNAL=Frontiers in Microbiology VOLUME=14 YEAR=2023 URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2023.1175679 DOI=10.3389/fmicb.2023.1175679 ISSN=1664-302X ABSTRACT=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 (PrPC) in immune cells.

Methods

Here, we investigated whether HTLV-1 infection affected PrPC 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 PrPC 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 PrPC, which was reflected by IFN type II but not IL-17 expression.

Discussion

These results suggested that PrPC 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.