Killing of Kaposi's sarcoma-associated herpesvirus-infected fibroblasts during latent infection by activated natural killer cells.
Killing of Kaposi's sarcoma-associated herpesvirus-infected fibroblasts during latent infection by activated natural killer cells.
复制标题
DOI：
10.1002/eji.201040661
复制
发表时间：
2011-07
影响因子：
5.4
通讯作者：
Gotch, Frances M.
中科院分区：
文献类型：
--
作者：
Matthews, Nick C.;Goodier, Martin R.;Robey, Rebecca C.;Bower, Mark;Gotch, Frances M.
卡波西肉瘤相关疱疹病毒（KSHV）通过逃避宿主免疫系统的清除而建立终身感染。在从头感染和裂解性复制中，KSHV通过下调I类MHC和ICAM-1分子以及参与形成和维持免疫突触的相关抗原来逃避细胞毒性T细胞和NK细胞。然而，在卡波西肉瘤（KS）病变中报告的主要潜伏性KSHV感染的背景下，这些机制的疗效尚不清楚。在一种新的慢性潜伏性KSHV感染的体外模型中使用原代真皮成纤维细胞，我们产生了与从KS病变中提取的梭形细胞中的病毒载量相似的靶细胞。我们发现，潜伏性KSHV感染的成纤维细胞具有正常水平的MHC-I类，ICAM-1，HLA-E和NKG 2D配体表达，对NK细胞的天然细胞毒性有抵抗力，并且对由精氨酸激活的免疫活性NK细胞的杀伤高度敏感。KSHV感染的成纤维细胞表达正常水平的IFN-γR1，并通过上调MHC I类分子、ICAM-1和HLA-E以及抵抗活化的NK细胞杀伤来应答外源性IFN-γ。这些数据表明，在原代细胞中潜伏KSHV感染的生理相关水平导致静息NK细胞的有限激活，并赋予激活的NK细胞的控制很少的特异性抗性。
Kaposi's sarcoma-associated herpesvirus (KSHV) establishes life-long infection by evading clearance by the host immune system. In de novo infection and lytic replication, KSHV escapes cytotoxic T cells and NK cells through downregulation of MHC class-I and ICAM-1 molecules and associated antigens involved in forming and sustaining the immunological synapse. However, the efficacy of such mechanisms in the context of the predominantly latent KSHV infection reported in Kaposi's sarcoma (KS) lesions is unclear. Using primary dermal fibroblasts in a novel in vitro model of chronic latent KSHV infection, we generated target cells with viral loads similar to those in spindle cells extracted from KS lesions. We show that latently KSHV-infected fibroblasts had normal levels of MHC-class I, ICAM-1, HLA-E and NKG2D ligand expression, were resistant to NK-cell natural cytotoxicity and were highly susceptible to killing by cytokine-activated immunocompetent NK cells. KSHV-infected fibroblasts expressed normal levels of IFN-γR1 and responded to exogenous IFN-γ by upregulating MHC class I, ICAM-1 and HLA-E and resisting activated NK-cell killing. These data demonstrate that physiologically relevant levels of latent KSHV infection in primary cells cause limited activation of resting NK cells and confer little specific resistance to control by activated NK cells.
登录
查看更多内容
影响因子：
5.4
作者：
Llano, M;Gumá, M;López-Botet, M
通讯作者：
López-Botet, M
影响因子：
3.7
作者：
Chang, J;Renne, R;Ganem, D
通讯作者：
Ganem, D
DOI：
10.1016/0190-9622(90)70169-i
发表时间：
1990-06-01
影响因子：
13.8
作者：
FRIEDMANKIEN, AE;SALTZMAN, BR
通讯作者：
SALTZMAN, BR
影响因子：
20.3
作者：
Davis, DA;Rinderknecht, AS;Yarchoan, R
通讯作者：
Yarchoan, R
影响因子：
20.3
作者：
Gumá, M;Angulo, A;López-Botet, M
通讯作者：
López-Botet, M