Human cytomegalovirus UL47 tegument protein functions after entry and before immediate-early gene expression.
The human cytomegalovirus UL47 open reading frame encodes a 110-kDa protein that is a component of the virion tegument. We have constructed a cytomegalovirus mutant, ADsubUL47, in which the central portion of the UL47 open reading frame has been replaced by two marker genes. The mutant replicated to titers 100-fold lower than those for wild-type virus after infection at either a high or a low input multiplicity in primary human fibroblasts but was substantially complemented on cells expressing UL47 protein. A revertant virus in which the mutation was repaired, ADrevUL47, replicated with wild-type kinetics. Mutant virions lacked UL47 protein and contained reduced amounts of UL48 protein. The mutant was found to be less infectious than wild-type virus, and a defect very early in the replication cycle was observed. Transcription of the viral immediate-early 1 gene was delayed by 8 to 10 h. However, this delay was not the result of a defect in virus entry or of the inability of virion proteins to transactivate the major immediate-early promoter. We also show that the UL47 protein coprecipitated with the UL48 and UL69 tegument proteins and the UL86-encoded major capsid protein. We propose that a UL47-containing complex is involved in the release of viral DNA from the disassembling virus particle and that the loss of UL47 protein causes this process to be delayed.
Bechtel
Jill T
JT
Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544-1014, USA.
Shenk
Thomas
T
D002213:Capsid / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology; D015870:Gene Expression; D017781:Genes, Immediate-Early; D005814:Genes, Viral; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics*; D008561:Membrane Fusion / Q000502:physiology; D016296:Mutagenesis; D011233:Precipitin Tests; D014158:Transcription, Genetic; D014764:Viral Proteins / Q000502:physiology*; D014771:Virion / Q000378:metabolism
C088645:IE1 protein, cytomegalovirus; D017874:Immediate-Early Proteins; C446319:UL47 protein, cytomegalovirus; D014764:Viral Proteins