Role of Integrin Signaling Activation on the Development of Human T Cell Leukemia Virus-1 (HTLV-1)-Associated Myelopathy/Tropical Spastic Paraparesis: Its Relationship to HTLV-1-Infected CD4+T Cell Transmigrating Activity into the Tissues

2018 ◽  
Vol 34 (4) ◽  
pp. 331-336 ◽  
Author(s):  
Tatsufumi Nakamura ◽  
Katsuya Satoh ◽  
Hideki Nakamura ◽  
Naomi Fukushima ◽  
Yoshihiro Nishiura ◽  
...  
Blood ◽  
1998 ◽  
Vol 91 (7) ◽  
pp. 2467-2474 ◽  
Author(s):  
Alan Lau ◽  
Simon Nightingale ◽  
Graham P. Taylor ◽  
Timothy W. Gant ◽  
Alan J. Cann

Overexpression of P-glycoprotein (P-gp), the protein product of the multidrug resistance gene (MDR1), confers a drug resistant phenotype on cells. This phenotype is reminiscent of human T-cell leukemia virus (HTLV)-transformed leukemic cells, for which no consistently effective chemotherapeutic regime has been found. The presence of an active multiple drug resistance (MDR) phenotype in freshly isolated peripheral blood mononuclear cells (PBMC) from HTLV-I–infected subjects was investigated. Significant P-gp–mediated efflux activity and enhanced MDR1 mRNA expression was observed in nine of 10 HTLV-infected subjects. The development of MDR phenotypes was found to be independent of disease type or status with significant MDR activities being observed in adult T-cell leukemia (ATL), HTLV-associated myelopathy (HAM)/tropical spastic paraparesis (TSP), and asymptomatic HTLV-infected individuals. P-gp–mediated drug efflux was also found to be restricted to CD3+ T-cell populations. Furthermore, we show the novel finding that theMDR1 gene promoter is transcriptionally activated by the HTLV-I tax protein, suggesting a molecular basis for the development of drug resistance in HTLV-I infections. These observations open up the possibility of new chemotherapeutic approaches to HTLV-associated diseases through the use of P-gp inhibitors.


Retrovirology ◽  
2014 ◽  
Vol 11 (Suppl 1) ◽  
pp. P83
Author(s):  
Aline CA Mota-Miranda ◽  
Fernanda K Barreto ◽  
Maria FC Amarante ◽  
Everton Baptista ◽  
Joana P Monteiro-Cunha ◽  
...  

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Mineki Saito ◽  
Charles R. M. Bangham

Human T-cell leukemia virus type-1 (HTLV-1) is a replication-competent human retrovirus associated with two distinct types of disease only in a minority of infected individuals: the malignancy known as adult T-cell leukemia (ATL) and a chronic inflammatory central nervous system disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HAM/TSP is a chronic progressive myelopathy characterized by spastic paraparesis, sphincter dysfunction, and mild sensory disturbance in the lower extremities. Although the factors that cause these different manifestations of HTLV-1 infection are not fully understood, accumulating evidence from host population genetics, viral genetics, DNA expression microarrays, and assays of lymphocyte function suggests that complex virus-host interactions and the host immune response play an important role in the pathogenesis of HAM/TSP. Especially, the efficiency of an individual's cytotoxic T-cell (CTL) response to HTLV-1 limits the HTLV-1 proviral load and the risk of HAM/TSP. This paper focuses on the recent advances in HAM/TSP research with the aim to identify the precise mechanisms of disease, in order to develop effective treatment and prevention.


2011 ◽  
Vol 286 (36) ◽  
pp. 31092-31104 ◽  
Author(s):  
Batsukh Dorjbal ◽  
David Derse ◽  
Patricia Lloyd ◽  
Ferri Soheilian ◽  
Kunio Nagashima ◽  
...  

1992 ◽  
Vol 31 (11) ◽  
pp. 1257-1261 ◽  
Author(s):  
Luis CARTIER ◽  
Fernando ARAYA ◽  
Jose Luis CASTILLO ◽  
Fernando RUIZ ◽  
Adriana GORMAZ ◽  
...  

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