JVI Accepts, published online ahead of print on 4 November 2009

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J. Virol. doi:10.1128/JVI.01961-09
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Adeno-associated virus type 5 (AAV5) utilizes alternative translation initiation to encode a small Rep40-like protein.

K. David Farris and David J. Pintel^*

Department of Molecular Microbiology and Immunology, University of Missouri-Columbia, School of Medicine, Bond Life Sciences Center, Columbia, MO

^* To whom correspondence should be addressed. Email: pinteld{at}missouri.edu.

Alternative splicing of AAV2 P19-generated pre-mRNAs generates the small Rep proteins Rep52 and Rep40, which differ in their carboxyl termini. Both proteins are required for optimal packaging of AAV2 genomes. AAV5 Rep-encoding P19-generated transcripts are primarily polyadenylated within its central intron and not efficiently spliced; however, surprisingly, AAV5 was found to generate high levels of a Rep40-like protein. The AAV5 Rep40-like protein was generated by internal initiation and shares the same C-terminus as Rep52. Although precluded from using alternative splicing to generate multiple Rep isoforms, AAV5 ensures production of a Rep40-like protein by utilizing a novel internal translation initiation event.