Human cytomegalovirus uses two distinct pathways to enter retinal pigmented epithelial cells

Dai Wang, Qian Chun Yu, Jörg Schröer, Eain Murphy, Thomas Shenk

Research output: Contribution to journalArticle

56 Scopus citations

Abstract

Human cytomegalovirus infects multiple cell types, including fibroblasts and epithelial cells. It penetrates fibroblasts by fusion at the cell surface but is endocytosed into epithelial cells. In this report, we demonstrate by electron microscopy that the virus uses two different routes to enter retinal pigmented epithelial cells, depending on the cell type in which the infecting virus was produced. Virus produced in epithelial cells preferentially fuses with the plasma membrane, whereas fibroblast-derived virus mostly enters by receptor-mediated endocytosis. Treatment of epithelial cells with agents that block endosome acidification inhibited infection by virus produced in fibroblasts but had only a modest effect on infection by virus from epithelial cells. Epithelial cell-generated virions had higher intrinsic "fusion-from-without" activity than fibroblast-generated particles, and the two virus preparations triggered different cellular signaling responses, as evidenced by markedly different transcriptional profiles. We propose that the cell type in which a human cytomegalovirus particle is produced likely influences its subsequent spread and its contribution to pathogenesis.

Original languageEnglish (US)
Pages (from-to)20037-20042
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number50
DOIs
StatePublished - Dec 11 2007

All Science Journal Classification (ASJC) codes

  • General

Keywords

  • Host cell transcriptome
  • Pathogenesis
  • Virus spread

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