Department of Pathobiology, School of Veterinary Medicine, Shiraz University, Shiraz, Iran.
Shiraz Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
Gene. 2023 Aug 20;878:147567. doi: 10.1016/j.gene.2023.147567. Epub 2023 Jun 15.
BK polyomavirus (BKPyV) infection in immunocompromised patients can led to polyomavirus-associated nephropathy (BKPyVAN) especially after kidney transplantation. The polyomavirus genome contains enhancer elements that are important transcription activators. In this study, the association between viral and host gene expression and NCCR variations was evaluated in kidney transplant recipients (KTRs) with BKPyV active, and BKPyV in-active infection.
Blood samples were collected from selected KTRs who divided to patients with active and in-active BKPyV infection. Transcriptional control region (TCR) anatomy was compared to the genomic sequence of archetype BKPyV strain WW using nested PCR method and sequencing. The expression level of some transcription factor genes was evaluated using in-house Real-time PCR (SYBR Green) technique. Most changes were observed after TCR anatomy detection in the Q and P blocks. The expression level of VP1 and LT-Ag viral genes were significantly higher in patients with active infection compared with non-infected ones. Transcription factor genes SP1, NF1, SMAD, NFκB, P53, PEA3, ETS1, AP2, NFAT and AP1 were significantly higher in BKPyV active group in comparison in-active and control groups. The analyses revealed that viral load level and mutations frequency has significant correlation.
Based on the results, increasing of NCCR variations were associated with higher viral load of BKPyV especially in Q block. Host transcriptional factors and viral genes all had higher express level in active BKPyV patients versus no in-active ones. Detection of the relation between NCCR variation and BKPyV severity in KTRs need to be confirmed in further complicated studies.
在免疫功能低下的患者中，BK 多瘤病毒（BKPyV）感染可导致多瘤病毒相关性肾病（BKPyVAN），尤其是在肾移植后。多瘤病毒基因组包含增强子元件，这些元件是重要的转录激活因子。在这项研究中，评估了具有 BKPyV 活性和非活性感染的肾移植受者（KTR）中病毒和宿主基因表达与 NCCR 变异之间的关系。
从选定的 KTR 中采集血液样本，这些 KTR 分为 BKPyV 活性感染和非活性感染患者。使用巢式 PCR 方法和测序比较转录控制区（TCR）解剖与原型 BKPyV 株 WW 的基因组序列。使用内部实时 PCR（SYBR Green）技术评估某些转录因子基因的表达水平。在 TCR 解剖检测后，大多数变化发生在 Q 和 P 块中。与未感染的患者相比，活性感染患者的 VP1 和 LT-Ag 病毒基因的表达水平明显更高。与非活性和对照组相比，BKPyV 活性组的转录因子基因 SP1、NF1、SMAD、NFκB、P53、PEA3、ETS1、AP2、NFAT 和 AP1 的表达水平明显更高。分析表明，病毒载量水平和突变频率具有显著相关性。
基于这些结果，NCCR 变异的增加与 BKPyV 的病毒载量升高有关，尤其是在 Q 块中。与非活性 BKPyV 患者相比，活性 BKPyV 患者的宿主转录因子和病毒基因表达水平均更高。在进一步复杂的研究中需要确认 NCCR 变异与 KTR 中 BKPyV 严重程度之间的关系。
