肿瘤病毒在人类中的致癌作用

StephenW

Oncogenic Role of Tumor Viruses in Humans

To cite this article:
Akram Nimrah, Imran Muhammad, Noreen Mamoona, Ahmed Fayyaz, Atif Muhammad, Fatima Zareen, and Bilal Waqar Ahmed. Viral Immunology. January 2017, 30 (1): 20-27. Doi: 10.1089 / vim.2016.0109.

Published in Volume: 30 Issue 1: January 1, 2017
Online Ahead of Print: November 10, 2016

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Author information
Nimrah Akram, 1 Muhammad Imran, 1 Mamoona Noreen, 2 Fayyaz Ahmed, 1 Muhammad Atif, 1 Zareen Fatima, 3 and Ahmed Bilal Waqar1
1Department of Medical Laboratory Sciences (DMLS), Faculty of Health and Allied Sciences (FHAS), Imperial College of Business Studies (ICBS), Lahore, Pakistan.
2Department of Zoology, The Women University Multan, Multan, Pakistan.
3Department of Radiological Sciences and Medical Imaging (DRSMI), FHAS, ICBS, Lahore, Pakistan.
Address correspondence to:
Dr. Muhammad Imran
Department of Medical Laboratory Sciences (DMLS)
Faculty of Health and Allied Sciences (FHAS)
Imperial College of Business Studies (ICBS)
Lahore 54000
Pakistan
E-mail: [email protected]
ABSTRACT

Viruses are the intracellular pathogens that reproduce only in the living cell and manipulate the cellular machinery to produce more viruses. Viral replications can affect cellular genes of the host in multiple cancerous ways. Approximately, 20% of all human oncogenesis is caused by cancer-causing As well as the major host cells are transformed into cancerous cells on the basis of host genetic variability. . Oncogenic viruses encode genes that cause viral replication and transformation of the host cells to produce viral proteins and protein complexes. From the basic viral infection to tumorigenesis is length of due to the involvement of factors like Fas complications, cellular mutations, and exposure to other (HCV), Epstein-Barr virus (EBV), Human papilloma virus (HPV), Kaposi's sarcoma herpes virus (KSHV), Hepatitis B virus (HBV), Hepatitis C virus (HCV) And Human T lymphotrophic virus 1 (HTLV-1). This review article summarizes advanced knowledge related to human oncogenic viruses and the molecular mechanisms that lead to tumorigenesis in humans.

StephenW

肿瘤病毒在人类中的致癌作用

引用本文：
Akram Nimrah，Imran Muhammad，Noreen Mamoona，Ahmed Fayyaz，Atif Muhammad，Fatima Zareen和Bilal Waqar Ahmed。病毒免疫学。 2017年1月，30（1）：20-27。 Doi：10.1089 / vim.2016.0109。

发布于第30卷第1期：2017年1月1日
在线版：2016年11月10日

全文HTML全文PDF（377.5 KB）全文PDF链接（342.5 KB）

作者信息
Nimrah Akram，1 Muhammad Imran，1 Mamoona Noreen，2 Fayyaz Ahmed，1 Muhammad Atif，1 Zareen Fatima，3和Ahmed Bilal Waqar1
1巴基斯坦拉合尔医学实验室科学（DMLS），卫生和相关科学学院（FHAS），帝国商业研究学院（ICBS）。
动物学部，妇女大学Multan，Multan，巴基斯坦。
3D放射科学和医学成像（DRSMI），FHAS，ICBS，拉合尔，巴基斯坦。
地址对应：
穆罕默德·伊姆兰博士
医学实验室科学系（DMLS）
健康与相关科学学院（FHAS）
帝国商学院（ICBS）
拉合尔54000
巴基斯坦
电子邮件：[email protected]
抽象

病毒是仅在活细胞中繁殖并操纵细胞机器产生更多病毒的细胞内病原体。病毒复制可以以多种癌症方式影响宿主的细胞基因。大约20％的所有人肿瘤形成是由癌症引起的以及主要宿主细胞基于宿主遗传变异性转化为癌细胞。 。致癌病毒编码引起病毒复制和宿主细胞转化以产生病毒蛋白和蛋白复合物的基因。从基本的病毒感染到肿瘤发生是由于涉及诸如Fas并发症，细胞突变和暴露于其它（HCV），EB病毒（EBV），人乳头状瘤病毒（HPV），卡波西氏肉瘤疱疹病毒（KSHV），乙型肝炎病毒（HBV），丙型肝炎病毒（HCV）和人淋巴细胞性病毒1（HTLV-1）。这篇综述文章总结了与人类致癌病毒相关的高级知识和导致人类肿瘤发生的分子机制。

StephenW

Hepatitis B virus

HBV is a partially double-stranded DNA virus. HBV was diagnosed as a serum-borne infective jaundice in 1940 (11). HBV is highly contagious and may be transmitted by exposure to HBV-infected blood and other body fluids through breaks in cutaneous and mucosal membrane. HBV infection is usually asymptomatic in adults, while it becomes chronic in young children or neonates (53). Chronicity with HBV has a major role in the development of hepatocellular carcinoma (HCC), and antiviral drugs are used to reduce HBV DNA levels to mitigate the possibility of HCC. HBV integrates its DNA into the host cellular genome causing mutations and accelerating liver inflammation (38). The precise pathologic mechanism of HBV infection is not completely understood. None of HBV proteins has been directly linked with acute oncogenic activity as the process of HCC development is a multistep complicated process that spans several decades (26). HBV encoded X antigen (HBx), a transcriptional activator of host cellular genes that is involved in HCC development. HBx activates specific cyclins, cyclin-dependent pathways, JAK/STAT pathway, and mitogen-activated protein kinase (MAPK) pathway leading to liver carcinogenesis due to interruption of tumor suppressor genes as shown in Figure 4 (17).

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FIG. 4.  Role of HBx in HCC development: Hepatits B X-antigen induces host cell genome instability and altered expression of various cytokines leading to antiviral state. HCC, hepatocellular carcinoma.
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A recent report of mice studies has shown the oncogenic role of HBx protein in the induction of HCC. Only HBx does not cause the cancers, but c-myc involvement leads to the development of cancer. HBx protein only acts as a promoter in tumor induction (60).

HBx causes p53 suppression that promotes the inactivation of pRb and also downregulates various CDK inhibitors (70). The involvement of tumor-associated fetal protein (AFP) action in HBx generating oncogenesis is also reported. The study on 614 HCC patients revealed that AFP is an intracellular signaling molecule acting as a probable participator in HBx inducing carcinogenesis (71). It is reviewed that recurrence of tumors is a dominating obstacle for diagnostic improvement of HBV-related HCC. Major viral factors for hepatic carcinoma recurrence include HBsAg, HBeAg, HBV DNA levels, and HBcAg (48).

StephenW

乙型肝炎病毒

HBV是部分双链DNA病毒。 HBV在1940年被诊断为血清传染性黄疸（11）。 HBV是高度传染性的，并且可以通过暴露于HBV感染的血液和其他体液通过皮肤和粘膜膜的破裂而传播。 HBV感染通常在成人中无症状，而在幼儿或新生儿中变为慢性（53）。与HBV的长期性在肝细胞癌（HCC）的发展中具有重要作用，并且抗病毒药物用于降低HBV DNA水平以减轻HCC的可能性。 HBV将其DNA整合到宿主细胞基因组中，引起突变和加速肝脏炎症（38）。 HBV感染的精确病理机制尚未完全了解。由于HCC发展过程是跨越几十年的多步复杂过程，所以没有一种HBV蛋白与急性致癌活性直接相关（26）。 HBV编码的X抗原（HBx），参与HCC发展的宿主细胞基因的转录激活子。 HBx激活特异性细胞周期蛋白，细胞周期蛋白依赖性通路，JAK / STAT途径和促分裂原活化蛋白激酶（MAPK）途径，由于肿瘤抑制基因的中断导致肝癌发生，如图4（17）所示。

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图。 HBx在HCC发展中的作用：Hepatits B X抗原诱导宿主细胞基因组不稳定性和改变导致抗病毒状态的各种细胞因子的表达。 HCC，肝细胞癌。
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最近的小鼠研究报告显示HBx蛋白在诱导HCC中的致癌作用。只有HBx不导致癌症，但c-myc参与导致癌症的发展。 HBx蛋白仅作为肿瘤诱导中的启动子（60）。

HBx引起p53抑制，其促进pRb的失活并且也下调多种CDK抑制剂（70）。也报道了肿瘤相关的胎儿蛋白（AFP）作用参与HBx产生肿瘤发生。对614例HCC患者的研究表明，AFP是一种细胞内信号分子，作为HBx诱导致癌作用的可能参与者（71）。它被审查，肿瘤的复发是诊断改善HBV相关肝癌的主要障碍。肝癌复发的主要病毒因子包括HBsAg，HBeAg，HBV DNA水平和HBcAg（48）

StephenW

http://online.liebertpub.com/doi/full/10.1089/vim.2016.0109