Holt Michael P, Shevach Ethan M, Punkosdy George A
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD , USA.
Front Oncol. 2013 Nov 26;3:287. doi: 10.3389/fonc.2013.00287.
Mouse Mammary Tumor Viruses are beta-retroviruses that exist in both exogenous (MMTV) and endogenous (Mtv) forms. Exogenous MMTV is transmitted via the milk of lactating animals and is capable of inducing mammary gland tumors later in life. MMTV has provided a number of critical models for studying both viral infection as well as human breast cancer. In addition to the horizontally transmitted MMTV, most inbred mouse strains contain permanently integrated Mtv proviruses within their genome that are remnants of MMTV infection and vertically transmitted. Historically, Mtv have been appreciated for their role in shaping the T cell repertoire during thymic development via negative selection. In addition, more recent work has demonstrated a larger role for Mtv in modulating host immune responses due to its peripheral expression. The influence of Mtv on host response has been observed during experimental murine models of Polyomavirus- and ESb-induced lymphoma as well as Leishmania major and Plasmodium berghei ANKA infection. Decreased susceptibility to bacterial pathogens and virus-induced tumors has been observed among mice lacking all Mtv. We have also demonstrated a role for Mtv Sag in the expansion of regulatory T cells following chronic viral infection. The aim of this review is to summarize the latest research in the field regarding peripheral expression of Mtv with a particular focus on their role and influence on the immune system, infectious disease outcome, and potential involvement in tumor formation.
小鼠乳腺肿瘤病毒是β逆转录病毒，以外源（MMTV）和内源（Mtv）两种形式存在。外源性MMTV通过泌乳动物的乳汁传播，能够在动物后期诱发乳腺肿瘤。MMTV为研究病毒感染和人类乳腺癌提供了许多关键模型。除了水平传播的MMTV外，大多数近交系小鼠品系在其基因组中都含有永久整合的Mtv前病毒，这些前病毒是MMTV感染的残余物并通过垂直传播。从历史上看，Mtv因其在胸腺发育过程中通过阴性选择塑造T细胞库的作用而受到关注。此外，最近的研究表明，由于Mtv在外周的表达，它在调节宿主免疫反应中发挥着更大的作用。在多瘤病毒和ESb诱导的淋巴瘤以及硕大利什曼原虫和伯氏疟原虫ANKA感染的实验小鼠模型中，观察到了Mtv对宿主反应的影响。在缺乏所有Mtv的小鼠中，观察到对细菌病原体和病毒诱导肿瘤的易感性降低。我们还证明了Mtv Sag在慢性病毒感染后调节性T细胞扩增中的作用。这篇综述的目的是总结该领域关于Mtv外周表达的最新研究，特别关注它们在免疫系统、传染病结局以及肿瘤形成潜在参与方面的作用和影响。
