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Journal of Virology, February 2004, p. 1782-1791, Vol. 78, No. 4
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.4.1782-1791.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Activation of the Early-Late Switch in Adenovirus Type 5 Major Late Transcription Unit Expression by L4 Gene Products

Daniel C. Farley, Jason L. Brown,{dagger} and Keith N. Leppard*

Department of Biological Sciences, University of Warwick, Coventry, CV4 7AL, United Kingdom

Received 15 August 2003/ Accepted 14 October 2003

The adenovirus major late transcription unit (MLTU) encodes multiple proteins from five regions, L1 to L5, through differential splicing and polyadenylation. MLTU expression is temporally regulated; only a single product from L1 (52/55K) is expressed prior to replication, but a subsequent switch, the mechanism of which has not been defined, leads to full expression that encompasses L1 IIIa and all L2 to L5 products. Transfection of a plasmid containing the complete MLTU gave a full array of proteins in proportions similar to those in a late infection, and in a time course, the temporal pattern of expression in a natural infection was reproduced. However, a plasmid truncated after the L3 poly(A) site exclusively expressed the L1 52/55K protein and was defective in the switch to full gene expression from L1 to L3. The L4 33K protein, supplied in trans, was sufficient to upregulate cytoplasmic mRNA for MLTU products characteristic of the late pattern of expression to levels comparable to those produced by the full-length MLTU. There was a corresponding increase in expression of the L1 IIIa, L2, and L3 proteins, except hexon. Hexon protein expression additionally required both the L4 100K protein in trans and sequences downstream of the L3 poly(A) site in cis. These results indicate that induction of L4 protein expression is a key event in the early-late switch in MLTU expression, which we propose is precipitated by small amounts of L4 expression in a feed-forward activation mechanism.

* Corresponding author. Mailing address: Department of Biological Sciences, University of Warwick, Coventry, CV4 7AL, United Kingdom. Phone: 44 (0)24 7652 3579. Fax: 44 (0)24 7652 3701. E-mail: Keith.Leppard{at}warwick.ac.uk.

{dagger} Present address: BioVex Ltd., Abingdon, OX14 4RX, United Kingdom.

Journal of Virology, February 2004, p. 1782-1791, Vol. 78, No. 4
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.4.1782-1791.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

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