Evolving evidence implicates cytomegalovirus as a promoter of malignant glioma pathogenesis.
Evolving evidence implicates cytomegalovirus as a promoter of malignant glioma pathogenesis.
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DOI：
10.1186/2042-4280-2-10
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发表时间：
2011-10-26
期刊：
影响因子：
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通讯作者：
Cobbs CS
中科院分区：
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作者：
Cobbs CS
人巨细胞病毒(HCMV)于2002年首次被报道与人类恶性胶质瘤密切相关。巨细胞病毒是一种疱疹病毒，可导致先天性脑感染和免疫受损个体的多器官疾病。恶性胶质瘤是最常见和最具侵袭性的成人脑肿瘤，而恶性多形性胶质母细胞瘤(GBM)是最高级别的胶质瘤，其预期寿命不到两年。巨细胞病毒基因产物编码多种蛋白质，可促进多种信号通路对肿瘤生长至关重要，包括那些参与有丝分裂、突变、细胞凋亡、炎症、血管生成、侵袭和免疫逃避的信号通路。几个研究小组现已证实，人类恶性胶质瘤普遍感染HCMV，并表达可促进胶质瘤发病机制中关键信号通路的基因产物。在这篇综述中，我讨论了我们和其他人最近发现在活体GBM中表达的特定的HCMV基因产物，包括HCMV IE1、US28、GB和IL-10蛋白。讨论了这些巨细胞病毒基因产物在胶质瘤生物学中的关键通路失调中所起的作用，包括PDGFR、AKT、STAT3和单核细胞/小胶质细胞功能。最后，我回顾了基于抗巨细胞病毒策略的新近出现的针对GBM的临床试验。
Human cytomegalovirus (HCMV) was first reported to be strongly associated with human malignant gliomas in 2002. HCMV is a herpesvirus that causes congenital brain infection and multi-organ disease in immumocompromised individuals. Malignant gliomas are the most common and aggressive adult brain tumors and glioblastoma multiforme (GBM), the highest grade glioma, is associated with a life expectancy of less than two years. HCMV gene products encode for multiple proteins that can promote the various signaling pathways critical to tumor growth, including those involved in mitogenesis, mutagenesis, apoptosis, inflammation, angiogenesis, invasion and immuno-evasion. Several groups have now demonstrated that human malignant gliomas are universally infected with HCMV and express gene products that can promote key signaling pathways in glioma pathogenesis. In this review I discuss specific HCMV gene products that we and others have recently found to be expressed in GBM in vivo, including the HCMV IE1, US28, gB and IL-10 proteins. The roles these HCMV gene products play in dysregulating key pathways in glioma biology, including the PDGFR, AKT, STAT3, and monocyte/microglia function are discussed. Finally, I review emerging human clinical trials for GBM based on anti-HCMV strategies.