Acha-Orbea Hans, Shakhov Alexander N, Finke Daniela
Department of Biochemistry, University of Lausanne, Ch. des Boveresses 155, CH-1066 Epalinges, Switzerland.
Front Biosci. 2007 Jan 1;12:1594-609. doi: 10.2741/2172.
Mouse mammary tumor virus (MMTV) has developed a strategy of exploitation of the immune response. It infects dendritic cells and B cells and requires this infection to establish an efficient chronic infection. This allows transmission of infection to the mammary gland, production in milk and infection of the next generation via lactation. The elaborate strategy developed by MMTV utilizes several key elements of the normal immune response. Starting with the infection and activation of dendritic cells and B cells leading to the expression of a viral superantigen followed by professional superantigen-mediated priming of naive polyclonal T cells by dendritic cells and induction of superantigen-mediated T cell B cell collaboration results in long-lasting germinal center formation and production of long-lived B cells that can later carry the virus to the mammary gland epithelium. Later in life it can induce transformation of mammary gland epithelium by integrating close to proto-oncogenes leading to their overexpression. Genes encoding proteins of the Wnt-pathway are preferential targets. This review will put these effects in the context of a normal immune response and summarize important facts on MMTV biology.
小鼠乳腺肿瘤病毒(MMTV)已经形成了一种利用免疫反应的策略。它感染树突状细胞和B细胞,并且需要这种感染来建立高效的慢性感染。这使得感染能够传播到乳腺,在乳汁中产生,并通过哺乳感染下一代。MMTV所发展出的精妙策略利用了正常免疫反应的几个关键要素。从树突状细胞和B细胞的感染与激活开始,导致病毒超抗原的表达,随后由专业的超抗原介导幼稚多克隆T细胞的致敏,以及树突状细胞诱导超抗原介导的T细胞与B细胞协作,从而导致持久的生发中心形成和长寿B细胞的产生,这些B细胞随后可以将病毒携带到乳腺上皮。在生命后期,它可以通过整合到原癌基因附近导致其过度表达,从而诱导乳腺上皮的转化。Wnt信号通路的蛋白质编码基因是优先靶点。本综述将把这些效应置于正常免疫反应的背景下,并总结MMTV生物学的重要事实。