title: The adenovirus L4-33K protein regulates both late gene expression patterns and viral DNA packaging.
abstract: The adenovirus (Ad) L4-33K protein has been linked to disparate functions during infection. L4-33K is a virus-encoded alternative RNA splicing factor which activates splicing of viral late gene transcripts that contain weak 3' splice sites. Additionally, L4-33K has been indicated to play a role in adenovirus assembly. We generated and characterized an Ad5 L4-33K mutant virus to further explore its function(s) during infection. Infectivity, viral genome replication, and most viral gene expression of the L4-33K mutant virus are comparable to those of the wild-type virus, except for a prominent decrease in the levels of the late proteins IIIa and pVI. The L4-33K mutant virus produces only empty capsids, indicating a defect in viral DNA packaging. We demonstrate that L4-33K does not preferentially bind to viral packaging sequences in vivo, and mutation of L4-33K does not interfere with the binding of the known viral packaging proteins IVa2, L4-22K, L1-52/55K, and IIIa to the packaging sequences in vivo. Collectively, these results demonstrate that the phenotype of an Ad5 L4-33K mutant virus is complex. The L4-33K protein regulates the accumulation of selective Ad late gene mRNAs and is involved in the proper transition of gene expression during the late phase of infection. The L4-33K protein also plays a role in adenovirus morphogenesis by promoting the packaging of the viral genome into the empty capsid. These results demonstrate the multifunctional nature of the L4-33K protein and its involvement in several different and critical aspects of viral infection.
authors.affiliation: Department of Molecular Genetics and Microbiology, School of Medicine, Stony Brook University, Stony Brook, New York, USA.
authors.forename: Kai
authors.initials: K
authors.lastname: Wu
authors.forename: Diana
authors.initials: D
authors.lastname: Guimet
authors.forename: Patrick
authors.initials: P
authors.lastname: Hearing
mesh_terms: D000260:Adenoviruses, Human / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D002460:Cell Line; D042003:DNA Packaging; D004279:DNA, Viral / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015967:Gene Expression Regulation, Viral; D006801:Humans; D009154:Mutation; D017361:Viral Nonstructural Proteins / Q000378:metabolism*; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019065:Virus Assembly; D014779:Virus Replication
chemical_list: D004279:DNA, Viral; D017361:Viral Nonstructural Proteins; D014764:Viral Proteins
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