Zheng Hua-Chuan, Xue Hang, Zhang Cong-Yu
Department of Oncology and Central Laboratory, The Affiliated Hospital of Chengde Medical University, Chengde, China.
Cancer Center, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China.
Front Oncol. 2022 Sep 23;12:976577. doi: 10.3389/fonc.2022.976577. eCollection 2022.
JC polyomavirus (JCPyV) belongs to the human polyomavirus family. Based on alternative splicing, the early region encodes the large and small T antigens, while the late region encodes the capsid structural proteins (VP1, VP2, and VP3) and the agnoprotein. The regulatory transcription factors for JCPyV include Sp1, TCF-4, DDX1, YB-1, LCP-1, Purα, GF-1, and NF-1. JCPyV enters tonsillar tissue through the intake of raw sewage, inhalation of air droplets, or parent-to-child transmission. It persists quiescently in lymphoid and renal tissues during latency. Both TGF-β1 and TNF-α stimulates JCPyV multiplication, while interferon-γ suppresses the process. The distinct distribution of caspid receptors (α-2, 6-linked sialic acid, non-sialylated glycosaminoglycans, and serotonin) determines the infection capabilities of JCPyV virions, and JCPyV entry is mediated by clathrin-mediated endocytosis. In permissive cells, JCPyV undergoes lytic proliferation and causes progressive multifocal leukoencephalopathy, while its DNA is inserted into genomic DNA and leads to carcinogenesis in non-permissive cells. T antigen targets p53, β-catenin, IRS, Rb, TGF-β1, PI3K/Akt and AMPK signal pathways in cancer cells. Intracranial injection of T antigen into animals results in neural tumors, and transgenic mice develop neural tumors, lens tumor, breast cancer, gastric, Vater's, colorectal and pancreatic cancers, insulinoma, and hepatocellular carcinoma. Additionally, JCPyV DNA and its encoded products can be detected in the brain tissues of PML patients and brain, oral, esophageal, gastric, colorectal, breast, cervical, pancreatic, and hepatocellular cancer tissues. Therefore, JCPyV might represent an etiological risk factor for carcinogenesis and should be evaluated for early prevention, diagnosis, and treatment of cancers.
JC多瘤病毒（JCPyV）属于人多瘤病毒家族。基于可变剪接，早期区域编码大T抗原和小T抗原，而晚期区域编码衣壳结构蛋白（VP1、VP2和VP3）以及无义蛋白。JCPyV的调节转录因子包括Sp1、TCF-4、DDX1、YB-1、LCP-1、Purα、GF-1和NF-1。JCPyV通过摄入未经处理的污水、吸入飞沫或母婴传播进入扁桃体组织。在潜伏期，它在淋巴组织和肾组织中静止存在。转化生长因子-β1（TGF-β1）和肿瘤坏死因子-α（TNF-α）均刺激JCPyV增殖，而干扰素-γ则抑制这一过程。衣壳受体（α-2,6-连接唾液酸、非唾液酸化糖胺聚糖和血清素）的不同分布决定了JCPyV病毒粒子的感染能力，并且JCPyV的进入是由网格蛋白介导的内吞作用介导的。在允许性细胞中，JCPyV进行裂解性增殖并导致进行性多灶性白质脑病，而其DNA插入基因组DNA并在非允许性细胞中导致癌变。T抗原靶向癌细胞中的p53、β-连环蛋白、胰岛素受体底物（IRS）、视网膜母细胞瘤蛋白（Rb）、TGF-β1、磷脂酰肌醇-3激酶/蛋白激酶B（PI3K/Akt）和腺苷酸活化蛋白激酶（AMPK）信号通路。向动物颅内注射T抗原会导致神经肿瘤，转基因小鼠会发生神经肿瘤、晶状体肿瘤、乳腺癌、胃癌、壶腹癌、结直肠癌和胰腺癌、胰岛素瘤以及肝细胞癌。此外，在进行性多灶性白质脑病患者的脑组织以及脑、口腔、食管、胃、结直肠、乳腺、宫颈、胰腺和肝细胞癌组织中可以检测到JCPyV DNA及其编码产物。因此，JCPyV可能是致癌的一个病因危险因素，应针对癌症的早期预防、诊断和治疗进行评估。
