A ribonucleotide reductase homolog of cytomegalovirus and endothelial cell tropism.
Human cytomegalovirus infects vascular tissues and has been associated with atherogenesis and coronary restenosis. Although established laboratory strains of human cytomegalovirus have lost the ability to grow on vascular endothelial cells, laboratory strains of murine cytomegalovirus retain this ability. With the use of a forward-genetic procedure involving random transposon mutagenesis and rapid phenotypic screening, we identified a murine cytomegalovirus gene governing endothelial cell tropism. This gene, M45, shares sequence homology to ribonucleotide reductase genes. Endothelial cells infected with M45-mutant viruses rapidly undergo apoptosis, suggesting that a viral strategy to evade destruction by cellular apoptosis is indispensable for viral growth in endothelial cells.
Brune
W
W
Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA. wbrune@princeton.edu
Ménard
C
C
Heesemann
J
J
Koszinowski
U H
UH
D016475:3T3 Cells; D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D002460:Cell Line; D003588:Cytopathogenic Effect, Viral; D004251:DNA Transposable Elements; D004730:Endothelium, Vascular / Q000166:cytology* / Q000821:virology*; D005347:Fibroblasts / Q000821:virology; D016368:Frameshift Mutation; D015723:Gene Library; D005814:Genes, Viral; D051379:Mice; D008969:Molecular Sequence Data; D018146:Muromegalovirus / Q000235:genetics* / Q000254:growth & development / Q000502:physiology*; D016254:Mutagenesis, Insertional; D016366:Open Reading Frames; D010641:Phenotype; D012264:Ribonucleotide Reductases / Q000235:genetics* / Q000502:physiology; D014764:Viral Proteins; D014779:Virus Replication
D004251:DNA Transposable Elements; D014764:Viral Proteins; D012264:Ribonucleotide Reductases; C422747:m45 protein, Mouse cytomegalovirus 1