Courreges Maria Cecilia, Burzyn Dalia, Nepomnaschy Irene, Piazzon Isabel, Ross Susan R
Department of Microbiology and Abramson Family Cancer Center, University of Pennsylvania, 313 BRBII/III, 421 Curie Blvd., Philadelphia, PA 19104-6142, USA.
J Virol. 2007 Apr;81(8):3769-77. doi: 10.1128/JVI.02728-06. Epub 2007 Jan 31.
Mouse mammary tumor virus (MMTV) is a milk-transmitted betaretrovirus that causes mammary tumors in mice. Although mammary epithelial cells are the ultimate targets of MMTV, the virus utilizes components of the host immune system to establish infection. Previous studies indicated that dendritic cells play a role in MMTV infection. Here we show that dendritic cells are the first cells to be infected by MMTV in vivo and that they are capable of producing infectious virus that can be transmitted to other cell types. Moreover, upon contact with the virus, dendritic cells became more mature and migrated in response to the chemokine macrophage inflammatory protein 3beta. Finally, we demonstrate that targeted ablation of dendritic cells in vivo dramatically attenuated MMTV infection. These data indicate that MMTV infection of dendritic cells is critical to initial propagation of the virus in vivo.
小鼠乳腺肿瘤病毒(MMTV)是一种通过乳汁传播的β逆转录病毒,可在小鼠体内引发乳腺肿瘤。尽管乳腺上皮细胞是MMTV的最终靶标,但该病毒利用宿主免疫系统的成分来建立感染。先前的研究表明,树突状细胞在MMTV感染中发挥作用。在此我们表明,树突状细胞是体内首个被MMTV感染的细胞,并且它们能够产生可传播至其他细胞类型的传染性病毒。此外,在与病毒接触后,树突状细胞变得更加成熟,并响应趋化因子巨噬细胞炎性蛋白3β而迁移。最后,我们证明在体内靶向清除树突状细胞可显著减弱MMTV感染。这些数据表明,树突状细胞的MMTV感染对于该病毒在体内的初始传播至关重要。