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Journal of Virology, April 2009, p. 3049-3058, Vol. 83, No. 7
0022-538X/09/$08.00+0     doi:10.1128/JVI.02455-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Adenovirus Serotype 5 L4-22K and L4-33K Proteins Have Distinct Functions in Regulating Late Gene Expression{triangledown}

Susan J. Morris and Keith N. Leppard*

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

Received 28 November 2008/ Accepted 19 January 2009

Adenoviruses express up to 20 distinct mRNAs from five major late transcription unit (MLTU) regions, L1 to L5, by differential splicing and polyadenylation of the primary transcript. MLTU expression is regulated at transcriptional and posttranscriptional levels. The L4-33K protein acts as a splicing factor to upregulate several MLTU splice acceptor sites as the late phase progresses. The L4 region also expresses a 22K protein whose sequence is related to the sequence of L4-33K. L4-22K is shown here also to have an important role in regulating the pattern of MLTU gene expression. An adenovirus genome containing a stop codon in the L4-22K open reading frame expressed low levels of both structural and nonstructural late proteins compared to the wild-type (wt) adenovirus genome; a decrease in intermediate proteins, IVa2 and IX, was also observed. However, early protein synthesis and replication were unaffected by the absence of L4-22K. Intermediate and late protein expression was restored to wt levels by L4-22K expressed in trans but not by L4-33K. Increased MLTU promoter activity, resulting from stabilization of the transcriptional activator IVa2 by L4-22K, made a small contribution to this restoration of late gene expression. However, the principal effect of L4-22K was on the processing of MLTU RNA into specific cytoplasmic mRNA. L4-22K selectively increased expression of penton mRNA and protein, whereas splicing to create penton mRNA is known not to be increased by L4-33K. These results indicate that L4-22K plays a key role in the early-late switch in MLTU expression, additional to and distinct from the role of L4-33K.

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

{triangledown} Published ahead of print on 28 January 2009.

Journal of Virology, April 2009, p. 3049-3058, Vol. 83, No. 7
0022-538X/09/$08.00+0     doi:10.1128/JVI.02455-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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