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.
Highlights
Human cytomegalovirus (HCMV) is a large, complex DNA virus belonging to the Herpesviridae family
Since clinical strains like FIX and TR replicate slowly in human foreskin fibroblast (HFF) cells compared to Towne, we investigated whether the clinical gene products have an affect on viral major immediate-early (MIE) gene expression
To identify the viral open reading frames (ORFs) that affect the efficiency of viral replication, we focused on the 7 ORFs between UL133 and UL138b
Summary
Human cytomegalovirus (HCMV) is a large, complex DNA virus belonging to the Herpesviridae family. It establishes a lifelong latent infection in the majority of the human population [1]. Viral gene expression occurs in three temporal phases, designated immediate-early (IE), early, and late. Transcription of the IE genes is independent of any de novo viral protein synthesis. IE gene products activate early viral gene expression, inhibit apoptosis, and neutralize intrinsic and innate cellular immunity (Review in [3, 4]). Viral proteins participate in viral DNA synthesis. The late genes, which primarily encode structural proteins, are expressed after viral DNA replication
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