HUMAN CYTOMEGALOVIRUS (HCMV) IMMEDIATE-EARLY ENHANCER PROMOTER SPECIFICITY DURING EMBRYOGENESIS DEFINES TARGET TISSUES OF CONGENITAL HCMV INFECTION

被引:74
作者
KOEDOOD, M [1 ]
FICHTEL, A [1 ]
MEIER, P [1 ]
MITCHELL, PJ [1 ]
机构
[1] UNIV ZURICH, INST MOLEC BIOL 2, CH-8057 ZURICH, SWITZERLAND
关键词
D O I
10.1128/JVI.69.4.2194-2207.1995
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Congenital human cytomegalovirus (HCMV) infection is a common cause of deafness and neurological disabilities. Many aspects of this prenatal infection, including which cell types are infected and how infection proceeds, are poorly understood. Transcription of HCMV immediate-early (IE) genes is required for expression of all other HCMV genes and is dependent on host cell transcription factors. Cell type-specific differences in levels of IE transcription are believed to underlie differences in infection permissivity. However, DNA transfection experiments have paradoxically suggested that the HCMV major IE enhancer/promoter is a broadly active transcriptional element with little cell type specificity. In contrast, we show here that expression of a lacZ gene driven by the HCMV major IE enhancer/promoter -524 to +13 segment is restricted in transgenic mouse embryos to sites that correlate with known sites; of congenital HCMV infection in human fetuses. This finding suggests that the IE enhancer/promoter is a major determinant of HCMV infection sites in humans and that transcription factors responsible for its regulation are cell type-specifically conserved between humans and mice. The lacZ expression patterns of these transgenic embryos yield insight into congenital HCMV pathogenesis by providing a spatiotemporal map of the sets of vascular, neural, and epithelial cells that are likely targets of infection. These transgenic mice may constitute a useful model system for investigating IE enhancer/promoter regulation in vivo and for identifying factors that modulate active and latent HCMV infections in humans.
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页码:2194 / 2207
页数:14
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