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

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 (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.

SUBMITTER: Silva De Castro I 

PROVIDER: S-EPMC10449582 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature