Project name: Homo sapiens

Description: Human cytomegalovirus infects multiple cell types, including fi-broblasts and epithelial cells. It penetrates fibroblasts by fusion atthe cell surface but is endocytosed into epithelial cells. In thisreport, we demonstrate by electron microscopy that the virus usestwo different routes to enter retinal pigmented epithelial cells,depending on the cell type in which the infecting virus wasproduced. Virus produced in epithelial cells preferentially fuseswith the plasma membrane, whereas fibroblast-derived virusmostly enters by receptor-mediated endocytosis. Treatment ofepithelial cells with agents that block endosome acidificationinhibited infection by virus produced in fibroblasts but had only amodest effect on infection by virus from epithelial cells. Epithelialcell-generated virions had higher intrinsic ‘‘fusion-from-without’’activity than fibroblast-generated particles, and the two viruspreparations triggered different cellular signaling responses, asevidenced by markedly different transcriptional profiles. We proposethat the cell type in which a human cytomegalovirus particleis produced likely influences its subsequent spread and its contributionto pathogenesis.Keywords: cell type comparison, viral infection, cell tropism, viral entryOverall design: A single strain of Human Cytomegalovirus (HCMV), termed BADrUL131, was used to prepare viral stocks from either fibroblast cells or from endothelial cells. These viral preparations (fibroBADrUL131 and epiBADrUL131) were used to infect ARP-19 cells (Human retinal pigmented epithelial cells) for either 6 hours or 10 hours. Total RNA was collected, labeled and used to hybridize to Agilent whole genome oligo microarrays and were normalized to a control reference RNA pool.

Data type: Transcriptome or Gene expression

Sample scope: Multiisolate

Relevance: Medical

Release date: 2007-11-10

Last updated: 2007-11-09