Glutathione reductase system changes in HTLV-1 infected patients

Abstract

During chronic HTLV-1 infections oxidative stress occurs and contributes in viral pathogenesis. Glutaredoxin (Grx) system is one of the most effective antioxidant components. The system maintains the cellular redox and scavenges reactive oxygen species through the function of glutathione reductase (GR) enzyme, NADPH and reduced glutathione (GSH). This study was performed to investigate potential changes in GR gene expression and activity as well as GSH level, and their association with the viral load in HTLV-1 infection. Forty HTLV-1 seropositive patients divided into two groups: asymptomatic carriers (N = 20) and HAM/TSP (N = 20) with the same number of age and sex-matched healthy controls were recruited in this study. GR cellular gene expression and viral load in PBMCs were determined using Real-time PCR Technique. Enzyme activity and GSH level in sera were measured by commercial kits based on manufacturer's provided protocols. GR gene expression and GR enzyme activity, as well as GSH level, were significantly lower in HTLV-1 patients. A negative correlation between viral load and GR gene expression/enzyme activity was observed in HAM/TSP group. Similarly, a negative relationship between viral load and GSH levels was observed in both carrier and HAM/TSP groups. We also found that in profound complicated condition of HTLV-1 infection, HAM/TSP, Grx system components activity was significantly decreased compared to the controls. Such observation was not the case in clinically healthy HTLV-1 carriers. These findings may shed a light on the conditions contributing in pathogenesis of the complications and exacerbation of the disease in the HAM/TSP cases.

Supplementary information: The online version contains supplementary material available at 10.1007/s13337-022-00758-y.

Keywords: Glutaredoxin; Glutathione; Glutathione reductase; HTLV-1; Oxidative stress.

Fig. 1

qPCR validation for the relative expression (fold change) of the GR gene in the three studied groups. The error bars indicate standard deviation. The Kruskal Wallis test shows that the expression of the GR gene in the studied groups has a significant difference (P value < 0.001). The results of the Mann Whitney test for comparison between groups also show that there is a significant difference in gene expression between the control group and the carriers (P value < 0.001). Besides, the difference in gene expression between control groups and HAM/TSP was also significant (P value < 0.001) However, there was no significant difference between gene expression levels in carrier groups and HAM/TSP

Fig. 2

Serum GR activity among the three studied groups. The statistical test (Kruskal Wallis) shows that there is a significant difference between the level of enzyme activity in the studied groups (P value = 0.009). Intergroup comparison (Mann Whitney test) shows that the difference in enzyme activity reduction between the control group and HTLV-1 carriers was significant (P value = 0.04). There is also this significance between the control group and HAM/TSP (P value = 0.004); however, the reduction in enzyme activity between carrier groups and HAM/TSP was not significant (P value = 0.3)

Fig. 3

The levels of GSH (mg/L) in serum of three studied groups. The Kruskal Wallis test showing that there was a significant difference in GSH levels between the three groups studied (P value < 0.001). The Mann Whitney test also indicates that this difference between the control group and the carrier (P value < 0.001) and between the control group and HAM/TSP (P value < 0.001) was significant. But there is no significant difference between the carrier group and HAM/TSP (P value = 0.052)