Rapp F, Cory J M
Department of Microbiology and Immunology, Pennsylvania State University, College of Medicine, Hershey 17033.
Cancer Detect Prev. 1990;14(4):437-44.
Oncogenic transformation of normal cells and the establishment of transformed cells to form malignant tumors is a complex, multistep process influenced by viruses in multiple ways. The relationship between viruses and the immune system manifests itself, in part, through various roles of viruses in transformation of host cells, including cells of the immune system. A large number of viruses participate in oncogenic transformation of cells in many animal species. Candidates for oncogenic transformation in man are human T lymphotropic viruses I and II, certain human papillomavirus types, hepatitis B virus, and Epstein-Barr virus. Various mechanisms, which may overlap with one another, have been proposed to account for viral oncogenesis. These include introduction of a directly transforming viral gene, retroviral transduction of protooncogenes, mutagenesis, uncoupling of cellular protooncogene expression from normal regulatory controls, overexpression of normal cellular genes resulting from effects of viral cis- or trans-acting factors, and inactivation of tumor suppressor genes. A second critical area of interaction between viruses and the immune system is in the selection of transformed cells. When cell transformation is accompanied by expression of tumor antigens, the immune system may influence tumor cell establishment and selection of transformed cells for metastatic outgrowth. Finally, host well-being may be severely compromised when viruses infect cells of the immune system, leading to an inability to mount immunological responses specific for opportunistic microorganisms and for cells transformed by viruses or nonviral agents. Human immunodeficiency virus infection exemplifies this phenomenon, although other viruses also negatively affect the immune system. The role of normal immune responses in limiting tumor cell growth is evident from the increased incidence of malignancies in immunocompromised hosts.
正常细胞的致癌转化以及转化细胞形成恶性肿瘤的过程是一个复杂的多步骤过程，受到病毒的多种影响。病毒与免疫系统之间的关系部分通过病毒在宿主细胞（包括免疫系统细胞）转化中的各种作用得以体现。大量病毒参与多种动物物种细胞的致癌转化。人类致癌转化的候选病毒有人嗜T淋巴细胞病毒I型和II型、某些人乳头瘤病毒类型、乙型肝炎病毒以及爱泼斯坦 - 巴尔病毒。为解释病毒致癌作用，已提出了多种可能相互重叠的机制。这些机制包括引入直接转化的病毒基因、原癌基因的逆转录病毒转导、诱变、细胞原癌基因表达与正常调控控制的解偶联、病毒顺式或反式作用因子导致的正常细胞基因过表达以及肿瘤抑制基因的失活。病毒与免疫系统相互作用的第二个关键领域在于转化细胞的选择。当细胞转化伴随着肿瘤抗原的表达时，免疫系统可能会影响肿瘤细胞的建立以及选择转化细胞进行转移生长。最后，当病毒感染免疫系统细胞时，宿主的健康可能会受到严重损害，导致无法对机会性微生物以及由病毒或非病毒因子转化的细胞产生特异性免疫反应。人类免疫缺陷病毒感染就是这种现象的例证，尽管其他病毒也会对免疫系统产生负面影响。免疫功能低下宿主中恶性肿瘤发病率的增加表明了正常免疫反应在限制肿瘤细胞生长中的作用。
