title: The human cytomegalovirus UL133-138 gene locus attenuates the lytic viral cycle in fibroblasts.
abstract: The genomes of HCMV clinical strains (e.g. FIX, TR, PH, etc) contain a 15 kb region that encodes 20 putative ORFs. The region, termed ULb', is lost after serial passage of virus in human foreskin fibroblast (HFF) cell culture. Compared to clinical strains, laboratory strains replicate faster and to higher titers of infectious virus. We made recombinant viruses with 22, 14, or 7 ORFs deleted from the ULb' region using FIX and TR as model clinical strains. We also introduced a stop codon into single ORFs between UL133 and UL138 to prevent protein expression. All deletions within ULb' and all stop codon mutants within the UL133 to UL138 region increased to varying degrees, viral major immediate early RNA and protein, DNA, and cell-free infectious virus compared to the wild type viruses. The wild type viral proteins slowed down the viral replication process along with cell-free infectious virus release from human fibroblast cells.
authors: Department of Internal Medicine, University of Iowa, Iowa City, United States of America.
authors: Nirmal
authors: N
authors: Dutta
authors: Center for Biocatalysis and Bioprocessing, University of Iowa, Iowa City, United States of America.
authors: Philip
authors: P
authors: Lashmit
authors: Department of Internal Medicine, University of Iowa, Iowa City, United States of America.
authors: Jinxiang
authors: J
authors: Yuan
authors: Department of Internal Medicine, University of Iowa, Iowa City, United States of America; Iowa Veterans Affairs Healthcare System, Iowa City, United States of America.
authors: Jeffery
authors: J
authors: Meier
authors: Department of Microbiology, University of Iowa, Iowa City, United States of America.
authors: Mark F
authors: MF
authors: Stinski
mesh_terms: D002478:Cells, Cultured; D018388:Codon, Terminator; D003587:Cytomegalovirus / Q000235:genetics*; D004261:DNA Replication; D004279:DNA, Viral; D005347:Fibroblasts / Q000821:virology*; D017353:Gene Deletion; D015870:Gene Expression; D023061:Gene Order; D017781:Genes, Immediate-Early; D016679:Genome, Viral; D006801:Humans; D009154:Mutation; D016366:Open Reading Frames; D011995:Recombination, Genetic; D014158:Transcription, Genetic; D014764:Viral Proteins / Q000235:genetics*; D014779:Virus Replication / Q000235:genetics*
chemical_list: D018388:Codon, Terminator; D004279:DNA, Viral; D014764:Viral Proteins