MACROPHAGE MIGRATION INHIBITORY FACTOR (MIF) IN HUMAN T CELL LYMPHOTROPIC VIRUS TYPE 1 (HTLV-1) INFECTION

DUCASA N; BUCALA R; TRIFONE C; BIGLIONE M; BERINI C; BENENCIO P; LENG L; TURK G

Lima

Conferencia; XIX INTERNATIONAL CONFERENCE ONHUMAN RETROVIROLOGY HTLV AND RELATED VIRUSES; 2019

International Retrovirology Association

Introduction: Human T cell lymphotropic virus type 1 (HTLV-1) is a deltaretrovirus harboured by around ten million people worldwide. It is the etiological agent of HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) and Adult T cell Leukemia/Lymphoma (ATLL). Only around 2-5% of the infected individuals will develop either pathology. Macrophage Migration Inhibitory Factor (MIF) is a cytokine that regulates a wide range of pro-inflammatory immune responses. It has been implicated in the development of many inflammatory conditions such as lupus, type II diabetes; various types of cancer and viral infections including HIV-1.Objectives: This study aimed to determine the role of MIF in HTLV-1 infection both in vivo and in vitro. Specifically, MIF plasma levels were measured in HTLV-1 infected patients with different disease outcomes. Also, MIF effect on viral replication was evaluated in vitro.Methods: MIF detection ELISA tests were performed on 20 plasma samples from HTLV-1 asymptomatic patients (AP), 20 ATLL patients, 20 HAM/TSP patients and 15 from healthy donors (HD). MIF blockage on MT2 cell cultures was performed using an anti-MIF antibody and a MIF agonist. Tax expression was measured by intracellular flow cytometry at 24, 48, 72 and 96 hours post-treatmentResults: MIF plasma levels were significantly higher in all HTLV-1 positive groups compared to HD (mean 2.197 pg/ml). MIF concentration was highest in AP (mean 60.04 pg/ml; p=0.0003 vs HD), followed by those subjects diagnosed with ATLL (mean 55.05 pg/ml; p=0.001 vs HD) and HAM/TSP (mean 19.84 pg/ml; p=ns).MIF blocking in MT2 cell cultures resulted in a 41% reduction in Tax-positive cells at 96 hours post-treatment with a MIF antagonist when compared to the isotype control (p=0.0138). A lower reduction (14%) was obtained when using a MIF-neutralizing antibody.Conclusion: The concentration of MIF in the plasma of HTLV-1 infected patients was significantly elevated compared to HD, particularly in asymptomatic subjects. In vitro results suggest that MIF might be supporting viral replication. Altogether, these pilot data encourage further investigations in this field.