Human Cytomegalovirus Virion Protein Complex Required for Epithelial and Endothelial Cell Tropism

Human cytomegalovirus replicates in many different cell types, including epithelial cells, endothelial cells, and fibroblasts. However, laboratory strains of the virus, many of which were developed as attenuated vaccine candidates by serial passage in fibroblasts, have lost the ability to infect epi...

Full description

Saved in:
Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2005-12, Vol.102 (50), p.18153-18158
Main Authors: Wang, Dai, Shenk, Thomas
Format: Article
Language:English
Subjects:
Antibodies
Biological Sciences
Cytomegalovirus - genetics
Cytomegalovirus - metabolism
Endothelial cells
Epithelial cells
Epithelial Cells - physiology
Fibroblasts
Fibroblasts - metabolism
Glycoproteins
Human cytomegalovirus
Human umbilical vein endothelial cells
Humans
Immunoprecipitation
Infections
Membrane Glycoproteins - metabolism
Microbiology
Multiprotein Complexes - metabolism
Neutralization Tests
Open reading frames
Proteins
Species Specificity
Tropism - genetics
Vaccines
Viral Envelope Proteins - metabolism
Viral Proteins - metabolism
Virion - genetics
Virion - metabolism
Virions
Viruses
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Human cytomegalovirus replicates in many different cell types, including epithelial cells, endothelial cells, and fibroblasts. However, laboratory strains of the virus, many of which were developed as attenuated vaccine candidates by serial passage in fibroblasts, have lost the ability to infect epithelial and endothelial cells. Their growth is restricted primarily to fibroblasts, due to mutations in the UL131-UL128 locus. We now demonstrate that two products of this locus, pUL130 and pUL128, form a complex with gH and gL, but not gO. The AD169 laboratory strain, which lacks a functional UL131 protein, produces virions containing only the gH-gL-gO complex. An epithelial and endothelial cell tropic AD169 variant in which the UL131 ORF has been repaired, termed BADHJL131, produces virions that carry both gH-gL-gO and gH-gL-pUL128-p(JL130 complexes. Antibodies against pUL130 and pUL128 block infection of epithelial and endothelial cells by BADrUL131 and the fusion-inducing factor X clinical human cytomegalovirus isolate but do not affect the efficiency with which fibroblasts are infected.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0509201102