Smirnov Sergey V, Harbacheuski Ryhor, Lewis-Antes Anita, Zhu Hua, Rameshwar Pranela, Kotenko Sergei V
Department of Biochemistry and Molecular Biology, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, NJ 07103, USA.
Virology. 2007 Mar 30;360(1):6-16. doi: 10.1016/j.virol.2006.09.017. Epub 2006 Nov 17.
Mesenchymal stem cells (MSCs) in bone marrow (BM) regulate the differentiation and proliferation of adjacent hematopoietic precursor cells and contribute to the regeneration of mesenchymal tissues, including bone, cartilage, fat and connective tissue. BM is an important site for the pathogenesis of human cytomegalovirus (HCMV) where the virus establishes latency in hematopoietic progenitors and can transmit after reactivation to neighboring cells. Here we demonstrate that BM-MSCs are permissive to productive HCMV infection, and that HCMV alters the function of MSCs: (i) by changing the repertoire of cell surface molecules in BM-MSCs, HCMV modifies the pattern of interaction between BM-MSCs and hematopoietic cells; (ii) HCMV infection of BM-MSCs undergoing adipogenic or osteogenic differentiation impaired the process of differentiation. Our results suggest that by altering BM-MSC biology, HCMV may contribute to the development of various diseases.
骨髓中的间充质干细胞(MSCs)调节相邻造血前体细胞的分化和增殖,并有助于包括骨、软骨、脂肪和结缔组织在内的间充质组织的再生。骨髓是人类巨细胞病毒(HCMV)发病机制的重要部位,该病毒在造血祖细胞中建立潜伏状态,并在重新激活后可传播至邻近细胞。在这里,我们证明骨髓间充质干细胞允许HCMV进行 productive 感染,并且HCMV会改变间充质干细胞的功能:(i)通过改变骨髓间充质干细胞中细胞表面分子的种类,HCMV改变了骨髓间充质干细胞与造血细胞之间的相互作用模式;(ii)对正在进行脂肪生成或成骨分化的骨髓间充质干细胞进行HCMV感染会损害分化过程。我们的结果表明,通过改变骨髓间充质干细胞生物学特性,HCMV可能促成各种疾病的发展。