Possible Trace of HTLV-1 Virus in Modulation of Cbl-b, ITCH, andPP2A Suppressor Genes

Document Type : Original Article

Authors
Atefeh Bahavar 1
Abdolvahab Moradi 2
Hamed Mohammadi 3 , 4
Mehdi Norouzi 5
Sara Khodayar 6 , 7
Sayed-Hamidreza Mozhgani 4 , 6
Alijan Tabarraei 8
1 Department of Microbiology, School of Medicine, Golestan University of Medical Sciences, Gorgan, Iran
2  Infectious Diseases Research Center, Golestan University of Medical Sciences, Gorgan, Iran.
3 Department of Immunology, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran.
4 Non-Communicable Disease Research Center, Alborz University of Medical Sciences, Karaj, Iran.
5 Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
6 Department of Microbiology and Virology, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran.
7 Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran.
8 Infectious Diseases Research Center, Golestan University of Medical Sciences, Gorgan, Iran.
10.22088/IJMCM.BUMS.14.1.472
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.
Keywords
HTLV-1
E3