MRC-University of Glasgow Centre for Virus Research, 8 Church Street, Glasgow, G11 5JR, Scotland, United Kingdom.
Virology. 2011 May 25;414(1):83-90. doi: 10.1016/j.virol.2011.03.005. Epub 2011 Apr 8.
The cellular protein hypoxia-inducible factor 1 alpha (HIF-1α) was induced after infection of human fibroblasts with human cytomegalovirus (HCMV). HCMV irradiated with ultraviolet light (uv-HCMV) also elicited the effect, demonstrating that the response was provoked by interaction of the infecting virion with the cell and that viral gene expression was not required. Although induction of HIF-1α was initiated by an early event, accumulation of the protein was not detected until 9 hours post infection, with levels increasing thereafter. Infection with uv-HCMV resulted in increased abundance of HIF-1α-specific RNA, indicating stimulation of transcription. In addition, greater phosphorylation of the protein kinase Akt was observed, and the activity of this enzyme was required for induction of HIF-1α to occur. HIF-1α controls the expression of many cellular gene products; therefore the findings reveal new ways in which interaction of the HCMV particle with the host cell may cause significant alterations to cellular physiology.
细胞蛋白缺氧诱导因子 1 ɑ（HIF-1ɑ）在人成纤维细胞感染人巨细胞病毒（HCMV）后被诱导。经紫外线（uv-HCMV）照射的 HCMV 也能引发这种效应，表明这种反应是由感染病毒与细胞的相互作用引起的，而不需要病毒基因表达。尽管 HIF-1ɑ的诱导是由早期事件引发的，但直到感染后 9 小时才检测到蛋白质的积累，此后水平增加。感染 uv-HCMV 导致 HIF-1ɑ特异性 RNA 的丰度增加，表明转录受到刺激。此外，观察到蛋白激酶 Akt 的磷酸化程度增加，并且该酶的活性对于 HIF-1ɑ的诱导发生是必需的。HIF-1ɑ控制许多细胞基因产物的表达；因此，这些发现揭示了 HCMV 颗粒与宿主细胞相互作用可能导致细胞生理学发生重大变化的新途径。
