HTLV-1 infection in bone marrow mesenchymal stem cells isolated from HTLV-1 individuals

The characterization of cell types that are susceptible to HTLV-1 infection is essential to understand of the biology of virus infection and the pathophysiology of HTLV-related diseases. In the present study, we investigated bone marrow (BM) cells from asymptomatic carriers (HAC) and symptomatic HTLV-1 individuals. Initially, we observed an infiltrated of CD4⁺ T-cell lymphocytes in BM from HTLV-1 individuals when compared to healthy controls (p≤0.02). The proviral DNA of BM HTLV-1 CD4⁺ T cells revealed the presence of integrated provirus. The number of fibroblast progenitor cells, referred as colony-forming units-fibroblasts (CFU-F), were lower in HTLV-1 infected individuals (CFU-F per 5 x 10⁵ cells in HAM/TSP (2.1±1.6), HAC (7.5±2.1) compared to healthy controls (10.4±1.1). HTLV-1 BM mesenchymal stem cells (MSC) isolated showed surface expression of CD105, CD73, and CD90, absence of hematopoietic markers such as CD45, CD34, and CD14; and in vitro differentiation to adipogenic and osteogenic cells. Proviral HTLV-1 DNA was detected in MSC from all HTLV-1 patients and the levels ranged from 2.5 to 25.7 copies per 10⁵ cells. HTLV-1 MSC was also positive to HTLV-1 p19 protein as determined by confocal microscopy. The confirmation of active viral replication was performed in the concentrated supernatant obtained from MSC by real-time PCR of the pol and gag HTLV-1 gene. In conclusion, we suggest that HTLV-1 could infect and replicate in human MSC possibly by the contact with infected CD4⁺ T-cells.

Financial support

FUNDHERP, CTC/FAPESP, INCTC, and CNPq.