Genome concatenation contributes to the late gene expression defect of an adenovirus E4 mutant

Adenovirus mutants that lack the entire E4 region are severely defective for late gene expression. E4 mutant genomes are also concatenated by host double strand break repair (DSBR) proteins. We find that E4 mutant late gene expression improves in MO59J cells that fail to form genome concatemers. DSB...

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Bibliographic Details
Published in:Virology (New York, N.Y.) N.Y.), 2005-11, Vol.342 (2), p.286-296
Main Authors: Jayaram, Sumithra, Bridge, Eileen
Format: Article
Language:English
Subjects:
Adenoviridae - genetics
Adenoviridae - physiology
Adenovirus
Adenovirus E4 Proteins - genetics
Androstadienes - pharmacology
Cell Line
Concatemer
Damage response
DNA Repair Enzymes - antagonists & inhibitors
DNA Repair Enzymes - physiology
DNA-PKcs
Double strand break repair
Gene Expression Regulation, Viral - drug effects
HeLa Cells
Humans
Mutation
Protein Kinase Inhibitors - pharmacology
Virus Replication
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Summary:Adenovirus mutants that lack the entire E4 region are severely defective for late gene expression. E4 mutant genomes are also concatenated by host double strand break repair (DSBR) proteins. We find that E4 mutant late gene expression improves in MO59J cells that fail to form genome concatemers. DSBR kinase inhibitors interfere with genome concatenation and also stimulate late gene expression. Concatenation of E4 mutant genomes interferes with cytoplasmic accumulation of viral late messages and leads to reduced late protein levels and poor viral yields following high multiplicity infection. However, failure to concatenate viral genomes did not rescue either the DNA replication defect or virus yield following low multiplicity E4 mutant infection. Our results indicate that if the E4 mutant DNA replication defect is overcome by high multiplicity infection, concatenation of the replicated genomes by host DSBR interferes with viral late gene expression.
ISSN:0042-6822
1096-0341
DOI:10.1016/j.virol.2005.08.004