Nepomnaschy I, Buggiano V, Goldman A, Piazzon I
División Medicina Experimental, Academia Nacional de Medicina, Buenos Aires.
Medicina (B Aires). 1997;57(2):235-44.
Mouse mammary tumor virus (MMTV) is a type B retrovirus that is transmitted as an infectious milk-borne particle and that causes mammary carcinomas by insertional activation of cellular protooncogenes. Germ line infections result in endogenous Mtv proviruses integrated in the genome of most mouse strains. These endogenous proviruses have been integrated into the genomes of mice for only the past 3-5 million years. The open reading frame present in the 3' long terminal repeat (LTR) of the provirus encodes a superantigen (SAg) which is able to stimulate a large proportion of T cells sharing a common T-cell receptor beta chain variable domain (v beta). Expression of this SAg is critical to the MMTV life cycle. After expression of the SAg in B cells a significant number of T cells are recruited to respond to these MMTV infected cells. As a consequence both the T cells expressing the relevant TCR V beta domain and the infected B cells become activated and start dividing. This would facilitate integration of MMTV and amplify the number of virus infected lymphocytes. Most likely during lactation the mammary glands become receptive to viral infection. The presence of endogenous Mtvs induces an early clonal deletion of reactive T cells. For this reason it has been argued that the presence of these proviruses confers a selective advantage to the mouse population by protecting the host from infection with an exogenous MMTV coding for a cross-reactive SAg. However, recent results discussed herein suggest that Mtv proviruses may also be detrimental to the mouse population by participating in recombinations with exogenous MMTVs, giving rise to highly tumorigenic recombinant particles. These results are discussed in the light of recent reports suggesting the involvement of viral sequences with a high homology to MMTV in human mammary tumorigenesis.
小鼠乳腺肿瘤病毒（MMTV）是一种B型逆转录病毒，它以感染性的乳汁传播颗粒形式传播，并通过细胞原癌基因的插入激活引发乳腺癌。种系感染导致内源性Mtv前病毒整合到大多数小鼠品系的基因组中。这些内源性前病毒仅在过去300万至500万年中整合到小鼠基因组中。前病毒3'长末端重复序列（LTR）中存在的开放阅读框编码一种超抗原（SAg），它能够刺激很大一部分共享共同T细胞受体β链可变区（vβ）的T细胞。这种SAg的表达对MMTV的生命周期至关重要。SAg在B细胞中表达后，大量T细胞被募集来对这些受MMTV感染的细胞作出反应。结果，表达相关TCR Vβ结构域的T细胞和受感染的B细胞都被激活并开始分裂。这将促进MMTV的整合并扩大病毒感染淋巴细胞的数量。最有可能在哺乳期，乳腺对病毒感染变得易感。内源性Mtv的存在诱导反应性T细胞的早期克隆缺失。因此，有人认为这些前病毒的存在通过保护宿主免受编码交叉反应性SAg的外源性MMTV感染，赋予小鼠群体一种选择优势。然而，本文讨论的最新结果表明，Mtv前病毒也可能对小鼠群体有害，因为它们会与外源性MMTV发生重组，产生高度致瘤性的重组颗粒。根据最近的报道讨论了这些结果，这些报道表明与MMTV具有高度同源性的病毒序列参与了人类乳腺肿瘤发生。
