A cyclooxygenase-2 homologue encoded by rhesus cytomegalovirus is a determinant for endothelial cell tropism
A cyclooxygenase-2 homologue encoded by rhesus cytomegalovirus is a determinant for endothelial cell tropism
复制标题
DOI：
10.1128/jvi.78.22.12529-12536.2004
复制
发表时间：
2004-11-01
影响因子：
5.4
通讯作者：
Nelson, JA
中科院分区：
文献类型：
--
作者：
Rue, CA;Jarvis, MA;Nelson, JA
环氧合酶-2 （COX-2）是类二十烷合成途径中的细胞酶，介导花生四烯酸合成前列腺素。类二十烷酸在许多细胞过程中起着关键的调节作用，包括急性和慢性炎症反应、止血和先天免疫反应。人类巨细胞病毒（HCMV）不编码病毒COX-2亚型，但已被证明可诱导细胞COX-2表达。重要的是，尽管COX-2在CMV复制中的确切作用尚不清楚，但COX-2的诱导被证明对正常的HCMV复制至关重要。在早期的一项研究中，我们在恒河巨细胞病毒（RhCMV）基因组中发现了一个开放阅读框（Rh10），该框架编码一种与细胞COX-2高度同源的推定蛋白（指定为vCOX-2）。在目前的研究中，我们发现vCOX-2在RhCMV感染期间通过早期基因动力学表达，导致70 kda蛋白的产生。与病毒COX-2异构体的表达一致，细胞COX-2在RhCMV感染期间未被诱导表达。最后，对缺失vCOX-2的重组RhCMV的生长分析发现，vCOX-2是内皮细胞复制的关键决定因素。
Cyclooxygenase-2 (COX-2) is a cellular enzyme in the eicosanoid synthetic pathway that mediates the synthesis of prostaglandins from arachidonic acid. The eicosanoids function as critical regulators of a number of cellular processes, including the acute and chronic inflammatory response, hemostasis, and the innate immune response. Human cytomegalovirus (HCMV), which does not encode a viral COX-2 isoform, has been shown to induce cellular COX-2 expression. Importantly, although the precise role of COX-2 in CMV replication is unknown, COX-2 induction was shown to be critical for normal HCMV replication. In an earlier study, we identified an open reading frame (Rh10) within the rhesus cytomegalovirus (RhCMV) genome that encoded a putative protein (designated vCOX-2) with high homology to cellular COX-2. In the current study, we show that vCOX-2 is expressed with early-gene kinetics during RhCMV infection, resulting in production of a 70-kDa protein. Consistent with the expression of a viral COX-2 isoform, cellular COX-2 expression was not induced during RhCMV infection. Finally, analysis of growth of recombinant RhCMV with vCOX-2 deleted identified vCOX-2 as a critical determinant for replication in endothelial cells.