Vaccine Effect of Extracellular Vesicles from HTLV-1 Infected Cells

Abstract

Human T-cell Lymphotropic Virus, type 1 (HTLV-1) is a retrovirus that causes adult T-cell leukemia/lymphoma cancer as well as HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis. The number of estimated infections worldwide is between 10 to 20 million and the main areas of HTLV-1 infections are Japan, Africa, South America, Middle East, and the Caribbean. The main method of HTLV-1 transmission is through cell-to-cell contact, however, it has been shown that small membrane-bound vesicles, extracellular vesicles (EVs), contain viral products, which in turn promote viral spread. The current treatment options include chemotherapy and antiviral drugs which have a low success rate of less than 10 percent. Emerging avenues of HTLV-1 treatment include utilizing dendritic cells (DCs) for T-cell and B-cell immunity. Here, we looked into the characteristics and proteins of the HTLV-1 derived EVs to determine if a possible vaccine-like reaction would occur if we introduced the EVs to DCs.

The EVs were obtained from the HTLV-1 infected HUT102 cell line. The EVs were separated into three subgroups based on size using differential ultracentrifugation (DUC): 2k EVs (2,000xg), 10k EVs (10,000xg), 100k EVs (100,000xg). The contents of EVs were analyzed through western blotting and mass spectrometry. The 2k and 10k EVs contained oncogenic proteins contributing to disease transmission, however, the 100k EVs lacked many of the destructive proteins and could be utilized as a vaccine-like treatment. The 2k and 100k EVs were placed on differentiated DCs to determine a potential immune response. The DCs cytokine production was analyzed through western blotting to determine if T-cell and B-cell activation would occur. In conclusion, we found a possible vaccine-like treatment for HTLV-1 through the use of HTLV-1 infected cell EVs by means of DC activation. Future experiments should include expanding testing in vivo along with the replication of data because of the limited time frame.