Ehtiati Sajad, Youssefi Masoud, Rafatpanah Houshang, Mashkani Baratali, Khadem-Rezaiyan Majid, Zahedi Avval Farnaz
Department of Clinical Biochemistry, School of Medicine, Mashhad University of Medical Sciences, Mashhad, 917794-8564 Iran.
Department of Microbiology and Virology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Virusdisease. 2022 Mar;33(1):32-38. doi: 10.1007/s13337-022-00758-y. Epub 2022 Mar 22.
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.
The online version contains supplementary material available at 10.1007/s13337-022-00758-y.
在慢性人类嗜T淋巴细胞病毒1型(HTLV-1)感染期间,会发生氧化应激并参与病毒发病机制。谷氧还蛋白(Grx)系统是最有效的抗氧化成分之一。该系统通过谷胱甘肽还原酶(GR)、烟酰胺腺嘌呤二核苷酸磷酸(NADPH)和还原型谷胱甘肽(GSH)的作用维持细胞氧化还原状态并清除活性氧。本研究旨在调查GR基因表达和活性以及GSH水平的潜在变化,及其与HTLV-1感染中病毒载量的关系。本研究招募了40名HTLV-1血清阳性患者,分为两组:无症状携带者(N = 20)和热带痉挛性截瘫/脊髓病(HAM/TSP,N = 20),并选取了年龄和性别匹配的相同数量的健康对照。使用实时聚合酶链反应(PCR)技术测定外周血单核细胞(PBMC)中的GR细胞基因表达和病毒载量。血清中的酶活性和GSH水平通过基于制造商提供方案的商用试剂盒进行测量。HTLV-1患者的GR基因表达、GR酶活性以及GSH水平均显著降低。在HAM/TSP组中观察到病毒载量与GR基因表达/酶活性之间呈负相关。同样,在携带者和HAM/TSP组中均观察到病毒载量与GSH水平之间呈负相关。我们还发现,在HTLV-1感染的严重复杂情况(HAM/TSP)下,与对照组相比,Grx系统成分的活性显著降低。在临床健康的HTLV-1携带者中则未出现这种情况。这些发现可能有助于揭示导致HAM/TSP病例中疾病并发症发病机制和病情加重的条件。
在线版本包含可在10.1007/s13337-022-00758-y获取的补充材料。