STLV-1 Commonly Targets Neurons in the Brain of Asymptomatic Non-Human Primates

The human T-cell leukemia virus (HTLV)-1 is responsible for an aggressive neurodegenerative disease (HAM/TSP) and multiple neurological alterations. The capacity of HTLV-1 to infect central nervous system (CNS) resident cells, together with the neuroimmune-driven response, has not been well-established. Here, we combined the use of human induced pluripotent stem cells (hiPSC) and of naturally STLV-1-infected nonhuman primates (NHP) as models with which to investigate HTLV-1 neurotropism. Hence, neuronal cells obtained after hiPSC differentiation in neural polycultures were the main cell population infected by HTLV-1. Further, we report the infection of neurons with STLV-1 in spinal cord regions as well as in brain cortical and cerebellar sections of postmortem NHP. Additionally, reactive microglial cells were found in infected areas, suggesting an immune antiviral response. These results emphasize the need to develop new efficient models by which to understand HTLV-1 neuroinfection and suggest an alternative mechanism that leads to HAM/TSP. The human T-cell leukemia virus (HTLV)-1 is responsible for an aggressive neurodegenerative disease (HAM/TSP) and multiple neurological alterations. The capacity of HTLV-1 to infect central nervous system (CNS) resident cells, together with the neuroimmune-driven response, has not been well-established.

Automated summary

The human T-cell leukemia virus (HTLV)-1 is responsible for an aggressive neurodegenerative disease (HAM/TSP) and multiple neurological alterations. The ability of HTLV-1 to infect cells in the central nervous system (CNS) and the resulting neuroimmune response have not been well-established. Using human induced pluripotent stem cells (hiPSC) and naturally infected nonhuman primates (NHP) as models, neuronal cells derived from hiPSC differentiation in neural polycultures were identified as the primary cell population infected by HTLV-1. Additionally, neuronal infection with STLV-1 was observed in spinal cord regions, as well as in brain cortical and cerebellar sections of postmortem NHP. Reactive microglial cells were also found in the infected areas, suggesting an immune antiviral response. These findings highlight the importance of developing more efficient models to understand HTLV-1 neuroinfection and propose an alternative mechanism for HAM/TSP.