Phillips A J, Tomasec P, Wang E C, Wilkinson G W, Borysiewicz L K
Department of Medicine, University of Wales College of Medicine, Heath Park, Cardiff, CF4 4XN, Wales.
Virology. 1998 Oct 25;250(2):350-8. doi: 10.1006/viro.1998.9385.
During the course of a productive infection, human cytomegalovirus (HCMV) has a sophisticated relationship with its host cell. An increasing number of virus-encoded genes are being identified which act specifically to usurp or modulate functions in the host cell associated with transcriptional control, cell signalling, and protein synthesis. While HCMV infection is associated with a general upregulation of cellular gene expression, the expression a small subset of cellular proteins, including the MHC-1 heavy chain and fibronectin, is downregulated. This study now identifies two additional cellular proteins, aminopeptidase N (CD13) and neutral endopeptidase (CD10), that are downregulated during HCMV infection. While aminopeptidase N and neutral endopeptidase exhibit no significant sequence homology, both are expressed on the cell surface and have very similar enzymatic properties. HCMV infection was associated with reduced surface expression and enzyme activity of CD13 and CD10, an apparent decrease in the rate of synthesis of both proteins in metabolic-labelling experiments, and inhibited glycosylation of the nascent CD13 and CD10 polypeptide chains that were synthesized. Levels of CD10 poly A+ RNA were suppressed efficiently at all stages of virus infection; however, the reduction in CD13 poly A+ RNA levels was much less pronounced. This differential effect suggests that HCMV may be downregulating expression of CD10 and CD13 by independent mechanisms. Indeed, treatment of cells with an inhibitor of viral DNA synthesis blocks downregulation of CD13, whilst downregulation of CD10 is unaffected. While it is not yet clear what advantage is bestowed on the virus by downregulating expression of CD13 and CD10, aminopeptidases are known to have a role in peptide processing in both the MHC class I the MHC class II antigen presentation pathways.
在 productive 感染过程中，人巨细胞病毒（HCMV）与其宿主细胞存在复杂的关系。越来越多的病毒编码基因被鉴定出来，它们专门用于篡夺或调节宿主细胞中与转录控制、细胞信号传导和蛋白质合成相关的功能。虽然 HCMV 感染与细胞基因表达的普遍上调有关，但一小部分细胞蛋白的表达，包括 MHC-1 重链和纤连蛋白，却被下调。本研究现已鉴定出另外两种在 HCMV 感染期间被下调的细胞蛋白，氨肽酶 N（CD13）和中性内肽酶（CD10）。虽然氨肽酶 N 和中性内肽酶没有明显的序列同源性，但它们都在细胞表面表达且具有非常相似的酶学性质。HCMV 感染与 CD13 和 CD10 的表面表达降低及酶活性降低相关，在代谢标记实验中这两种蛋白的合成速率明显下降，并且新合成的 CD13 和 CD10 多肽链的糖基化受到抑制。在病毒感染的所有阶段，CD10 多聚腺苷酸 + RNA 的水平都被有效抑制；然而，CD13 多聚腺苷酸 + RNA 水平的降低则不太明显。这种差异效应表明 HCMV 可能通过独立机制下调 CD10 和 CD13 的表达。事实上，用病毒 DNA 合成抑制剂处理细胞可阻断 CD13 的下调，而 CD10 的下调不受影响。虽然目前尚不清楚下调 CD13 和 CD10 的表达会给病毒带来什么优势，但已知氨肽酶在 MHC I 类和 MHC II 类抗原呈递途径的肽加工中发挥作用。
