The immunoevasive function encoded by the mouse cytomegalovirus gene m152 protects the virus against T cell control in vivo
The immunoevasive function encoded by the mouse cytomegalovirus gene m152 protects the virus against T cell control in vivo
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DOI：
10.1084/jem.190.9.1285
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发表时间：
1999-11-01
影响因子：
15.3
通讯作者：
Koszinowski, UH
中科院分区：
文献类型：
--
作者：
Krmpotic, A;Messerle, M;Koszinowski, UH
巨细胞病毒编码了许多功能，这些功能抑制了主要组织相容性复合物（MHC）I类途径的抗原表现。一个例子是由M152基因编码的小鼠巨细胞病毒（MCMV）糖蛋白GP40，该基因在内质网中有选择地保留了鼠而不是人类MHC I类配合物，该复合物在内质网中 - 高尔基体中间隔间/CIS-GOLGI CACKERTMENT/CIS-GOLGI CARCATMENT（ZIEGLER）（Ziegler，Ziegler，Ziegler，R.R. Thale，P。Lucin，W。Muranyi，T。Flohr，H。Hengel，H。Farrell，W。Rawlinson和U.H.为了研究自然宿主MCMV感染期间该基因功能的体内意义，我们构建了MCMV的重组者，其中M152基因被删除，以及相应的病毒恢复，我们报告了以下发现：M152基因的缺失：M152基因的缺失对细胞培养的病毒复制没有影响，而在感染小鼠后，M152缺陷病毒复制以显着降低病毒滴度。通过将基因的重新插入到突变体中来提高这种衰减效果。突变体和恢复体在剥夺病毒基因功能靶向的功能的动物中生长到相同的滴度，即在缺乏β2-微球蛋白的小鼠中，CD8分子缺乏小鼠，而小鼠在T细胞中枯竭。将幼稚淋巴细胞传递到感染的小鼠中后，缺乏M152基因功能将病毒敏感到原发性淋巴细胞对照。这些：结果证明，MHC反应函数可保护CMV免受体内CD8（+）T淋巴细胞的攻击。
Cytomegaloviruses encode numerous functions that inhibit antigen presentation in the major histocompatibility complex (MHC) class I pathway in vitro. One example is the mouse cytomegalovirus (MCMV) glycoprotein gp40, encoded by the m152 gene, which selectively retains murine but not human MHC class I complexes in the endoplasmic reticulum-Golgi intermediate compartment/cis-Golgi compartment (Ziegler, H., R. Thale, P. Lucin, W. Muranyi, T. Flohr, H. Hengel, H. Farrell, W. Rawlinson, and U.H. Koszinowski. 1997. Immunity. 6:57-66). To investigate the in vivo significance of this gene function during MCMV infection of the natural host, we constructed recombinants of MCMV in which the m152 gene was deleted, as were the corresponding virus revertants, We report on the following findings: Deletion of the m152 gene has no effect on virus replication in cell culture, whereas after infection of mice, the m152-deficient virus replicates to significantly lower virus titers. This attenuating effect is Lifted by reinsertion of the gene into the mutant. Mutants and revertants grow to the same titer in animals deprived of the function targeted by the viral gene function, namely in mice deficient in beta 2-microglobulin, mice deficient in the CD8 molecule, and mice depleted of T cells. Upon adoptive transfer of naive lymphocytes into infected mice, the absence of the m152 gene function sensitizes the virus to primary lymphocyte control. These: results prove that MHC-reactive functions protect CMVs against attack by CD8(+) T lymphocytes in vivo.