Slobedman Barry, Stern J Lewis, Cunningham Anthony L, Abendroth Allison, Abate Davide A, Mocarski Edward S
Centre for Virus Research, Westmead Millennium Institute and University of Sydney, Westmead, New South Wales 2145, Australia.
J Virol. 2004 Apr;78(8):4054-62. doi: 10.1128/jvi.78.8.4054-4062.2004.
Herpesviruses establish lifelong latent infections in their hosts. Human cytomegalovirus (CMV) targets a population of bone marrow-derived myeloid lineage progenitor cells that serve as a reservoir for reactivation; however, the mechanisms by which latent CMV infection is maintained are unknown. To gain insights into mechanisms of maintenance and reactivation, we employed microarrays of approximately 26,900 sequence-verified human cDNAs to assess global changes in cellular gene expression during experimental CMV latent infection of granulocyte-macrophage progenitors (GM-Ps). This analysis revealed at least 29 host cell genes whose expression was increased and six whose expression was decreased during CMV latency. These changes in transcript levels appeared to be authentic, judging on the basis of further analysis of a subset by semiquantitative reverse transcription-PCR. This study provides a comprehensive snapshot of changes in host cell gene expression that result from latent infection and suggest that CMV regulates genes that encode proteins involved in immunity and host defense, cell growth, signaling, and transcriptional regulation. The host genes whose expression we found altered are likely to contribute to an environment that sustains latent infection.
疱疹病毒可在其宿主中建立终身潜伏感染。人巨细胞病毒（CMV）靶向一群骨髓来源的髓系祖细胞，这些细胞可作为病毒再激活的储存库；然而，潜伏性CMV感染得以维持的机制尚不清楚。为深入了解维持和再激活机制，我们使用了约26,900个经序列验证的人cDNA微阵列，以评估粒细胞-巨噬细胞祖细胞（GM-Ps）实验性CMV潜伏感染期间细胞基因表达的整体变化。该分析揭示，在CMV潜伏期间，至少有29个宿主细胞基因的表达增加，6个宿主细胞基因的表达减少。基于对一个子集进行半定量逆转录PCR的进一步分析判断，转录水平的这些变化似乎是真实的。本研究全面呈现了潜伏感染导致的宿主细胞基因表达变化，并表明CMV可调节编码参与免疫和宿主防御、细胞生长、信号传导及转录调控的蛋白质的基因。我们发现表达发生改变的宿主基因可能有助于维持潜伏感染的环境。
