Autophagy flux modulates Tax viral protein distribution pattern in human T-cell lymphotropic virus type 1 (HTLV-1) infection

Abstract Background Viruses can evade the host's immune response promoting their survival and proliferation by different mechanisms. It has recently been observed that viruses can also manipulate autophagy mechanism/pathway for their own benefit. Autophagy is a conserved catabolic process for intracellular components, such as proteins and organelles, and it is important in maintaining cellular homeostasis. Human T-cell lymphotropic virus type 1 (HTLV-1) is the causative agent of HTLV-1 associated Myelopathy/ Tropical Spastic Paraparesis (HAM/TSP), Adult T-cell Leukemia/Lymphoma (ATLL) and Bronchiectasis. HTLV-1 has been reported to regulate autophagy favoring viral production. Viral protein Tax blocks the fusion of the autophagosome with the lysosome, preventing degradation and increasing the accumulation of autophagosomes. Yet, the role of autophagy in HTLV-1 infection has not been fully described. The aim of this study was to determine if the autophagic state conditions regulate HTLV-1 infection. Results Tax was distributed in specific patterns and spherical structures in infected Jurkat, HeLa and MT2 cell lines. Autophagic flux treatments modified Tax behavior in infected HeLa and MT2 cell lines as analyzed by confocal microscopy and flow cytometry, respectively. Utilizing relative quantification of mRNA by qPCR, the variation of other viral genes was analyzed, observing a similar pattern for each treatment. Conclusions These results provide evidence that the autophagic state is shown to control HTLV-1 infection. In addition, Tax can be observed in spherical structures linked to the plasma membrane which could be involved in promoting viral propagation. By carrying out this research, we hope to elucidate fundamental mechanisms for the propagation of HTLV-1 that would involve the use of the autophagic pathway, providing a potential therapeutic target to prevent the development of pathologies associated with HTLV-1 infection.