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Journal of Virology, March 2007, p. 2205-2212, Vol. 81, No. 5
0022-538X/07/$08.00+0     doi:10.1128/JVI.02312-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Positive and Negative Effects of Adenovirus Type 5 Helper Functions on Adeno-Associated Virus Type 5 (AAV5) Protein Accumulation Govern AAV5 Virus Production{triangledown}

Ramnath Nayak and David J. Pintel*

Department of Molecular Microbiology and Immunology, University of Missouri—Columbia, School of Medicine, Life Sciences Center, Columbia, Missouri 65211

Received 20 October 2006/ Accepted 5 December 2006

Full replication of adeno-associated virus type 5 (AAV5) is sustained by adenovirus type 5 (Ad5) helper functions E1a, E1b, E2a, E4Orf6, and virus-associated (VA) RNA; however, their combined net enhancement of AAV5 replication was comprised of both positive and negative individual effects. Although Ad5 E4Orf6 was required for AAV5 genomic DNA replication, it also functioned together with E1b to degrade de novo-expressed, preassembled AAV5 capsid proteins and Rep52 in a proteosome-dependent manner. VA RNA enhanced accumulation of AAV5 protein, overcoming the degradative effects of E4Orf6, and was thus required to restore adequate amounts of AAV5 proteins necessary to achieve efficient virus production.

* Corresponding author. Mailing address: 471f Life Sciences Building, 1201 E. Rollins Rd., Columbia, MO 65211-7310. Phone: (573) 882-3920. Fax: (573) 884-9676. E-mail: pinteld{at}missouri.edu.

{triangledown} Published ahead of print on 13 December 2006.

Journal of Virology, March 2007, p. 2205-2212, Vol. 81, No. 5
0022-538X/07/$08.00+0     doi:10.1128/JVI.02312-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Nayak, R., Farris, K. D., Pintel, D. J. (2008). E4Orf6-E1B-55k-Dependent Degradation of De Novo-Generated Adeno-Associated Virus Type 5 Rep52 and Capsid Proteins Employs a Cullin 5-Containing E3 Ligase Complex. J. Virol. 82: 3803-3808 [Abstract] [Full Text]  
  • Nayak, R., Pintel, D. J. (2007). Adeno-Associated Viruses Can Induce Phosphorylation of eIF2{alpha} via PKR Activation, Which Can Be Overcome by Helper Adenovirus Type 5 Virus-Associated RNA. J. Virol. 81: 11908-11916 [Abstract] [Full Text]  


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