Possible Trace of HTLV-1 Virus in Modulation of Cbl-b, ITCH, and PP2A Suppressor Genes.

Abstract

For almost 40 years, human T-lymphotropic virus type 1 (HTLV-1) has posed a persistent challenge in managing the major diseases associated with HTLV-1. Intracellular inhibitors are critical regulators of T cell activation, and their function can be influenced by viruses. Because of less studied aspects of HTLV-1 in T cell activation, we evaluated three suppressor genes in patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and asymptomatic carriers (ACs). Thirty samples were collected from three groups from 10/09/2022 to 03/27/2024. To confirm all the samples, ELISA and PCR tests were done. The isolation of peripheral blood mononuclear cells (PBMCs), RNA extraction, and cDNA synthesis were conducted. Subsequently, the expression of Tax trans-activator, HTLV-1 bZIP factor (HBZ), protein phosphatase 2 A (PP2A), and two E3 ligases, including Casitas B lymphoma-b (Cbl-b) and itchy E3 Ubiquitin protein ligase (ITCH), was measured via Real-time PCR. This survey showed a significant increase in ITCH among individuals with HAM/TSP and ACs compared to the healthy group. The PP2A mRNA expression level was upregulated in the ACs; in contrast, the expression levels were approximately similar in the HAM/TSP and healthy groups. Also, the mean expression level of Cbl-b was higher in the ACs than in the other groups; however, it was not statistically significant. Our findings demonstrated that the intercellular suppressor genes could be dysregulated during the HTLV-1 infection, probably as part of the virus's strategic goals. The findings can be helpful for future investigation in the diagnosis and treatment area.