Abstract
BackgroundRecently, human T-cell leukemia virus type 1 (HTLV-1) basic leucine zipper factor (HBZ), encoded from a minus strand mRNA was discovered and was suggested to play an important role in adult T cell leukemia (ATL) development. However, there have been no reports on the role of HBZ in patients with HTLV-1 associated inflammatory diseases.ResultsWe quantified the HBZ and tax mRNA expression levels in peripheral blood from 56 HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients, 10 ATL patients, 38 healthy asymptomatic carriers (HCs) and 20 normal uninfected controls, as well as human leukemic T-cell lines and HTLV-1-infected T-cell lines, and the data were correlated with clinical parameters. The spliced HBZ gene was transcribed in all HTLV-1-infected individuals examined, whereas tax mRNA was not transcribed in significant numbers of subjects in the same groups. Although the amount of HBZ mRNA expression was highest in ATL, medium in HAM/TSP, and lowest in HCs, with statistical significance, neither tax nor the HBZ mRNA expression per HTLV-1-infected cell differed significantly between each clinical group. The HTLV-1 HBZ, but not tax mRNA load, positively correlated with disease severity and with neopterin concentration in the cerebrospinal fluid of HAM/TSP patients. Furthermore, HBZ mRNA expression per HTLV-1-infected cell was decreased after successful immunomodulatory treatment for HAM/TSP.ConclusionThese findings suggest that in vivo expression of HBZ plays a role in HAM/TSP pathogenesis.
Highlights
Human T-cell leukemia virus type 1 (HTLV-1) basic leucine zipper factor (HBZ), encoded from a minus strand mRNA was discovered and was suggested to play an important role in adult T cell leukemia (ATL) development
We investigated whether human T-cell leukemia virus type 1 (HTLV-1) HBZ mRNA expression is associated with clinical and laboratory markers reported in HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients, including HTLV-1 proviral load, neopterin concentration in cerebrospinal fluid (CSF), and motor disability score
We showed that the CSF neopterin level, which was positively correlated with proviral load, was positively correlated with the HBZ mRNA load in HAM/TSP patients (Spearman's rank correlation coefficient P = 0.0052, r = 0.437)
Summary
Human T-cell leukemia virus type 1 (HTLV-1) basic leucine zipper factor (HBZ), encoded from a minus strand mRNA was discovered and was suggested to play an important role in adult T cell leukemia (ATL) development. There have been no reports on the role of HBZ in patients with HTLV-1 associated inflammatory diseases. In HTLV-1 infection, approximately 5% develop ATL [7] and another 2%-3% develop chronic inflammatory diseases involving the central nervous system (HAM/ TSP), the eyes [8], the lungs [9], the joints [10], or the skeletal muscles [11]; most infected individuals, remain healthy in their lifetime (healthy asymptomatic carriers: HCs). We investigated whether HTLV-1 HBZ mRNA expression is associated with clinical and laboratory markers reported in HAM/TSP patients, including HTLV-1 proviral load, neopterin concentration in cerebrospinal fluid (CSF), and motor disability score. To confirm the previous observations [17,18], we have investigated the tax mRNA expression in ATL patients, HAM/TSP patients, and HCs by using the same technology but in a larger number of subjects
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