Characterization of the role of adenovirus-5 (Ad-5) gene products E2A, E4ORF6 and VA RNA on adeno-associated virus type 5 (AAV5) transcription, translation and replication
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[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT REQUEST OF AUTHOR.] AAV5 is the most distinct serotype of the AAVs differing from the prototype virus AAV2 at the nucleotide level. We show that in AAV5 the Rep transcripts terminate in the middle of the intron whereas in AAV2 the same transcripts read-through the proximal (intronic) polyadenylation site. Furthermore unlike in AAV2, the AAV5 promoters do not depend on adenovirus genes E2a, E4orf6 and VA RNA for efficient activation and pre-mRNA splicing. Inspite of these differences at the level of transcription between AAV5 and AAV2, we observed that efficient AAV5 virus production requires all five adenovirus gene products E1a, E1b-55k, E2a, E4orf6 and VA RNA. We find that E4orf6 has negative whereas VA RNA has positive effects on AAV5 Cap and small Rep protein production. E4orf6 functions like an E3 ligase complex to bring about degradation of capsid proteins whereas VA RNA inhibits the activation of PKR to augment capsid protein production.
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