Human T‐lymphotropic virus 1 (HTLV‐1) pathogenesis: A systems virology study

Abstract

The main mechanisms of interaction between Human T-lymphotropic virus type 1 (HTLV-1) and its hosts in the manifestation of the related disease including HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) and Adult T-cell leukemia/lymphoma (ATLL) are yet to be determined. It is pivotal to find out the changes in the genes expression toward an asymptomatic or symptomatic states. To this end, the systems virology analysis was performed. Firstly, the differentially expressed genes (DEGs) were taken pairwise among the four sample sets of Normal, Asymptomatic Carriers (ACs), ATLL, and HAM/TSP. Afterwards, the protein-protein interaction networks were reconstructed utilizing the hub genes. In conclusion, the pathways of cells proliferation and transformation were identified in the ACs state. In addition to immune pathways in ATLL, the inflammation and cancer pathways were discened in both diseases of ATLL and HAM/TSP. The outcomes can specify the genes involved in the pathogenesis and help to design the drugs in the future.

An insight to HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) pathogenesis; evidence from high-throughput data integration and meta-analysis

“…PSMB8 is one of the 17 subunits essential for the synthesis of the 20S proteasome unit (Akiyama et al, 1994). The targeting of proteasome in the HAM/TSP disease is a known mechanism to affect the pathogenicity of HTLV-1 by increasing the activity of genes such as IKBKG, which we have already reported (Mozhgani et al, 2018b). PSMB8 can affect the immune responses because one of the important actions of PSMB8 is involvement in the process of apoptosis (Yang et al, 2009), so its increase in patients with HAM/TSP may be due to this function.…”

“…PSMB8 can affect the immune responses because one of the important actions of PSMB8 is involvement in the process of apoptosis (Yang et al, 2009), so its increase in patients with HAM/TSP may be due to this function. Although previous studies reported the role of apoptosis in HAM/TSP pathogenesis (Mozhgani et al, 2018b), there is no comprehensive information regarding the role of PSMB8.…”

“…The sub-network clustering was implemented using the fast unfolding clustering algorithm in Gephi (Mozhgani et al, 2018b). The biologically meaningful modules were then chosen.…”

“…HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic neurodegenerative disease with progressive characteristics that disturbs the functioning of the sensory and motor nerves (Andrade et al, 2013). Indeed, infection with HTLV-1 can lead to asymptomatic carrier (AC) state or two diseases including Adult T-Cell Leukemia Lymphoma (ATLL) or/and HAM/TSP (Mozhgani et al, 2018b).…”

“…Since now, different genes that are involved in mTOR, NF-kappa B, PI3K, and MAPK signaling pathways have been known in the HAM/TSP cases. Also, apoptosis can occur in the cell nucleus of the HAM/TSP patients (Moriuchi et al, 1999;Ottoson et al, 2001;Mozhgani et al, 2018b).…”