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

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.host cell transcriptome ͉ pathogenesis ͉ virus spread

HCMV gH/gL/UL128–131 interferes with virus entry into epithelial cells: Evidence for cell type-specific receptors

“…The derivation of HCMV may also influence receptor usage and routes of infection. Wang and Shenk (43) reported that HCMV produced by epithelial cells more extensively infected epithelial cells in the presence of lysosomotropic agents compared with HCMV derived from fibroblasts. However, anti-UL130 antibodies blocked epithelialderived and fibroblast-derived HCMV, suggesting that gH/gL/ UL128-131 was essential in both cases.…”

Potent obatoclax cytotoxicity and activation of triple death mode killing across infant acute lymphoblastic leukemia

“…Pellets were fixed with prewarmed fixative (2.5% glutaraldehyde, 2% paraformaldehyde in sodium cacodylate) for 1 hour and processed. 20 Ultrathin sections were examined with a Jeol (Peabody, MA) JEM-1010 electron microscope fitted with an Advanced Microscopy Techniques (AMT) (Woburn, MA) digital camera with dedicated image acquisition software.…”

The susceptibility of primary cultured rhesus macaque kidney epithelial cells to rhesus cytomegalovirus strains

“…As viral determinants for HCMV entry of EP, UL128L-encoded proteins, form a pentamer with gH and gL mediating HCMV entry into EP via an endocytotic pathway (Bodaghi et al, 1999;Ryckman et al, 2008;Wang & Shenk, 2005;Wang et al, 2007). The UL128L is conserved in RhCMV, and its products are postulated to form a pentamer complex with RhCMV gH and gL (Wussow et al, 2013).…”

“…Proteins encoded by UL128L, together with glycoprotein H (gH) and L (gL), form a gH-anchored pentamer complex that mediates HCMV entry of EP and endothelial cells via receptor-dependent endocytosis. The genetic integrity of UL128L determines the level of virus entry, which, in turn, regulates the infectivity of HCMV in these cells (Bodaghi et al, 1999;Ryckman et al, 2006;Wang & Shenk, 2005;Wang et al, 2007). However, it has been noted that the anatomical and tissue origin of both EP and endothelial cells affects HCMV infection efficiency and pathogenesis (Esclatine et al, 2000;Fish et al, 1998;Jarvis & Nelson, 2007;Jarvis et al, 1999;Millard et al, 2010;Tugizov et al, 1996).…”