Evaluation of HTLV-I and Host Interaction on Development of Adult T-cell Leukemia/lymphoma: Study of HBZ, RORγt, FOXP3, BAD Genes Expression

Human T-lymphotropic virus type 1 (HTLV-I) infects more than 20 million people worldwide.About 2% to 5% of infected people may develop two HTLV-I accossiated diseases; Adult Tcellleukemia /lymphoma (ATLL) or HAM/TSP. Viral-host interactions are the main players ofdiseases development and progression. Therefore, HTLV-I bZIP factor (HBZ) as a humanimmunomodulator enable virus evasion from host immune responses and implicated inTCD4+ proliferation and ATLL progression. Moreover, regulatory T-cells as the main sourceof the virus, and Th17 as an inflammatory cell may be impaired toward diseasesmanifestation and progression. Also Inhibiting of pro-apoptotic elements such as BAD maybe induced by HTLV-1 as one step of oncogenic process. Therefore in the present study theexpression of HBZ, RORγt, FOXp3 and BAD genes have been evaluated. Nineteen patientswith ATLL and 18 HTLV-I healthy carriers were assessed for HBZ, RORγt FOXP3 and BADexpression using real time PCR, TaqMan method. The data was analyzed by SPSSsoftware. In the present study HBZ expression was dramatically increased in ATLL patientscompare to HTLV-I carriers (p-value< 0.000), and also RORγt expression was increased inATLL patients compare to HTLV-I carriers (p-value= 0.020). In the case of FOXP3 and BADno significant difference were found between 2 groups. Results showed that viral HBZ hadcritical role in HTLV-I infected TCD4+ immune evasion toward oncogenesis. Increasedexpression of RORγt, as a master transcription factor of Th17 consistent with inflammatoryreactions in skin and other organs of the patients. Our findings showed that regulatory T-cellscells were not functionally involved in ATLL progression. Moreover, not significantly increasein BAD expression indicated virus through inhibiting increase in pro-appototic proteinsconserves a malignant potency.

کلیدواژه ها:

Adult T-cell Leukemia /Lymphoma (ATLL) ، HBZ ، Regulatory T-cells ، Th17 ، BAD